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Thursday, November 6, 2008
Cake Headlines
Thursday, November 6, 2008
And that's how new categories are born, boys and girls.
Jen: [in announcer voice] "Today in Cake News: Better Art Through Cupcakes." [turning to face side camera] "The Buffalo News reported today that Zilly Rosen of ZILLYCAKES in Buffalo, NY, made a portrait of president-elect Obama using nothing but 1,240 cupcakes!"
Weather Guy: "Wow, that's a lot of cupcakes!"
Jen: "It sure is, Weather Guy. I guess you could call this one sweet piece of art!"
Both: "Ahahahahahah!"
Thanks to Jenny B. and Joy for sharing the link. And yes, before you all ask: I AM relieved that Zilly didn't connect the cupcakes to make the world's largest CCC. Talk about a close call!
83 comments | Post a Comment
- Chibi Kitten said...
*blink blink*
Now, THAT'S a lot of cupcakes. - November 6, 2008 at 12:24 PM
Wow - that's incredible! Did Zilly make that whole thing yesterday, or start early, with a little election optimism?
- November 6, 2008 at 12:30 PM
- Pamela Kirkpatrick said...
I really like it. A lot. That's genius right there.
-Pam - November 6, 2008 at 12:32 PM
- Ms Ashley said...
It's really amazing what they can do with cupcakes... This shows someone has some REAL cupcake talent!
- November 6, 2008 at 12:33 PM
- Mari said...
That is actually cool... in a matrixy digital kind of way!
- November 6, 2008 at 12:37 PM
- HorribleLicensePlates said...
I would like one of the three white teeth cupcakes to eat, thakyouverymuch.
- November 6, 2008 at 12:39 PM
- Megan said...
wow! It really looks like him too! That is something I could take a bite out of!
- November 6, 2008 at 12:43 PM
- Jen said...
That's awesome! I agree...good thing it wasn't one big CCC.
- November 6, 2008 at 12:46 PM
I must be tired... I don't see the resemblance.
- November 6, 2008 at 12:46 PM
- Brad said...
Why is his skin blue? Is it some kind of post-racial statement? A nod to the electoral college map?
- November 6, 2008 at 12:47 PM
Well íf Zilly made that whole thing in one day, she had superpowers - or she doesn't need sleep. Or maybe she started early - but made also one cupcake-thing of McCain!
- November 6, 2008 at 12:47 PM
- Vashti said...
INSANE!.....only in America!
- November 6, 2008 at 12:48 PM
- Becky said...
You are freakin' hilarious!
And yeah, that really hurts my eyes! - November 6, 2008 at 12:53 PM
Well, the cupcakes themselves could obviously be baked ahead of time. And given that each one is frosted in a single solid color, she could have done most, if not all, of that ahead of time too. (Another bonus of NOT frosting them all together as a CCC monstrosity!) And then later arranged them to form a digital "black and white" portrait of whichever candidate won. I suspect she chose blue because it's a little bit more appetizing than grey...or red, though I suppose I could see doing this in red-and-white for McCain.
- November 6, 2008 at 12:59 PM
- G said...
Talk about a sugar coma!
- November 6, 2008 at 1:03 PM
- An Apron Straitjacket said...
That really is cool!
- November 6, 2008 at 1:06 PM
- Marissa said...
- November 6, 2008 at 1:08 PM
- FreedomFirst said...
Wow, she did an nice job!
- November 6, 2008 at 1:20 PM
I love this blog, but I don't think you have to be quite so diplomatic. (I don't think you need a disclaimer at the top of a post about an Obama cupcake tribute.) Hopefully, your readership can handle something like this. Thanks!
- November 6, 2008 at 1:23 PM
Love this blog!
I've given your blog an award... check it out at bumblingbaker.blogspot.com.
Keep the wrecks coming! - November 6, 2008 at 1:29 PM
This is awesome, but there is a minor wreck here. Counting the bottom row and one of the columns in the middle shows that it's 38 x 32 which is 1216, not 1240.
Should've just stuck to "Over 1200 cupcakes!", but all that sugar is making me crazy :) - November 6, 2008 at 1:43 PM
Whos gonna eat all that????
- November 6, 2008 at 1:51 PM
- Jackie said...
Hey, that's cool! Nice work! Perhaps someone has been reading your blog. Wouldn't be surprised.
- November 6, 2008 at 2:00 PM
- alicia said...
i wonder who, if anyone, got to eat all those cupcakes?
- November 6, 2008 at 2:06 PM
- Kelli said...
Good lord anonymous, who cares, really? I don't think Jen was being anything, other than Jen – who by the way, we love!
And why is it always the snotty comments come from "anonymous?"
Regarding the cakes, would you call this is PC, as in "political cupcake?" - November 6, 2008 at 2:14 PM
- Hyena Overlord said...
Thats cool. You could psp a pic then blow the pixels up to figure out what colour goes where. Not that I'd want to.
At least its size prevents it from being a candidate for ccc punishment.
Now I want cupcakes. I'll have to go get some. - November 6, 2008 at 2:17 PM
- Unknown said...
That's awesome! I want to eat a cupcake from the tie.
- November 6, 2008 at 2:51 PM
That is really pretty cool!
- November 6, 2008 at 2:54 PM
The cupcakes at display at the Obama campaign headquarters in
Buffalo, so no McCain portrait. It was the front page picture in this mornings Buffalo News. - November 6, 2008 at 3:04 PM
- alexlady said...
WOW! to the cake, and...'wow'... to the friendly neighborhood news commentary. you know they were proud of themselves for that witticism. :)
www.alexladydesigns.etsy.com - November 6, 2008 at 3:13 PM
Thanks for the positive remarks, and in answer to your questions:
1. I started planning on Friday and Saturday, baked all of them on Sunday and Monday, worked with a friend to cover them all with Italian meringue buttercream and fondant circles on Monday until 10pm, set them up on Tuesday to photograph in my friend's studio, then set them up again on Wednesday at the Obama headquarters!
2. I used blue for the democrats, and made this to send my creative energy up into the "ether" in the days before the election in hopes of Obama's win. BTW, I only made Obama, and I would have set it up and served it even if he lost, in celebration of his historic campaign and in honor or all the volunteers and the work they did nationwide. Buffalo volunteers on his campaign took the cupcakes home and enjoyed them.
3. Yes, you clever counter! There were 1248 in the original design but my family ate too many chocolate ones unbeknownst to me, so I had to take off the bottom line of the design, thus 1216 cupcakes. Not even close to what I would call a wreck, though. If anyone was wondering, the background is vanilla cake w/ vanilla frosting but Obama is chocolate cake w/ vanilla icing. - November 6, 2008 at 3:15 PM
- Bri said...
I love that...a CCC that isn't deformed or scary looking!
- November 6, 2008 at 3:17 PM
- Rach said...
This looks strangely like pushpin art. Are you sure this is a bonafide CCC?
- November 6, 2008 at 3:19 PM
- Unknown said...
So...if you rearranged the cupcakes would it make a picture of McCain? Just to make sure he had the right picture either way the votes went.
- November 6, 2008 at 3:22 PM
This is a great use of what I would think was some kind of grid drawing blown up to ridiculous proportions. For all the time I'm sure it took, the artist(s) surely delivered! Great work!
- November 6, 2008 at 3:32 PM
- Jen said...
Hey, Zilly! Glad you found us over here. (And just to be clear, I don't consider your creation to be a Wreck at all!)
Hey hey HEY, now, everyone, let's not get all carried away calling this a CCC, mmmkay? It's a cupcake MOSAIC, NOT a cupcake-cake. Remember, CCC = bad. Non-connected cupcakes without mounds of goopy icing in all the cracks = gooood.
Glad we got that cleared up. Carry on! - November 6, 2008 at 3:48 PM
- Emily and Laura said...
It's great to see the finished portrait -- they showed Zilly in the process of very carefully setting it up on the NBC news in D.C. last night. I was really impressed -- it's great to see a CCC that's actually creative!
- November 6, 2008 at 3:56 PM
- Jessica R. said...
That is ridiculously cool! Wow!
- November 6, 2008 at 4:18 PM
- Dea said...
I am a former Buffalonian! :D I love it! I also love that Zilly did this for the volunteers, for the headquarters - win or lose, this was what she made! Love it! :D
And yeah - mosaic cupcakes = YAY, CCC = boooo! - November 6, 2008 at 4:36 PM
- Chelsea said...
That's pretty awesome!
What would have been cool is if they had given it more detail by coloring each cupcake with more than one color. It sounds like a pretty intense project, though. I give it two frosting-covered thumbs up! *licks frosting off thumbs* yum! - November 6, 2008 at 4:38 PM
- Topaz said...
I saw this on the news this morning and am glad to see it posted here! Definitely one of the most original cupcake ideas I have ever seen.
Kudos Zilly!
(And thanks Jen, for having such a FUN blog!) - November 6, 2008 at 4:38 PM
Awesome!! Kudos to the Creator...
This is a better link cuz it shows Zilly setting up...
http://www.flickr.com/photos/77637592@N00/sets/72157608661883041/ - November 6, 2008 at 4:52 PM
- Michele said...
Thanks for telling us, Zilly. I was really wondering if the cupcakes were chocolate. ; D
- November 6, 2008 at 5:14 PM
- Chris said...
No, no, no, this is all wrong. The cupcakes should be connected by a 2 inch thick sloppy sheet of unattractive, nauseating icing, and the image crudely drawn on top, with his name misspelled.
- November 6, 2008 at 5:28 PM
- Denise said...
That had to be hard to pull off. I really like it.
- November 6, 2008 at 5:39 PM
- Peggy said...
DANG!!!! I was all set to direct you to that story. I was gonna do it this morning but I was running late for work. Thats two now...the puzzle cake one and now this. I gotta be a little bit quicker on the uptake here
- November 6, 2008 at 6:25 PM
I love the concept and execution! It's like cupcake pointilism.
- November 6, 2008 at 6:47 PM
- Sarah :) said...
I love you.
So much. You make me laugh more then the cakes do, most of the time. (:
Ans someone has WAY to much time on their hands. And way to many cupcakes.
lifeastoldbysarah.blogspot.com - November 6, 2008 at 7:43 PM
A friend of my sis showed your blog to her; in turn, she showed it to me.
May I put a link of your site to my blog?
I have a feeling your website will be a hit. Such great idea about disastrous cakes. Makes me want to go out there and spot these disasters and send you pix.
However, I've never come across one. Except for one nearly birthday cake mistake I recently got for my 21 y.o. son. Check it out:
Thanks. - November 6, 2008 at 7:53 PM
- Boozy Tooth said...
Yeah but the only problem with the picture is... awww shucks, the election is over, still, right?
Alixandra Hice
http://casahice.blogspot.com - November 6, 2008 at 8:07 PM
- Ghost Rider said...
I'm pretty relieved that they didn't ice them all together too--that just kills any chance of it looking nice. I thought it looked neat.
- November 6, 2008 at 8:27 PM
- ella fae said...
The cupcake portrait matches up very well with his pop-art style adverts/signs--so yay for no CCCs. I'm always impressed when people can put together individual elements to make a larger picture.
- November 6, 2008 at 8:43 PM
Should we read something into the black and blue going on here?
Was chocolate not an option? - November 6, 2008 at 8:49 PM
- Unknown said...
Please...NO...not on my food too!
- November 6, 2008 at 9:20 PM
that is just too cool for words!!!
- November 6, 2008 at 10:43 PM
- erin k said...
Well I don't actually have anything to add, but the word verification is "gravel". Just thought I'd share...
- November 6, 2008 at 10:51 PM
- mints said...
that's right, BUFFALOOOO!!!
[fellow buffalonian] - November 6, 2008 at 11:34 PM
this is NOT a ccc! thank goodness!
cupcakes NOT connected by a sheet of sloppy frosting would be...wait for it...just cupcakes! which are wonderful. ;)
ccc = surefire wrecks
-bg - November 7, 2008 at 12:11 AM
- spackledorfed said...
our president-elect is delicious
- November 7, 2008 at 12:13 AM
- TB Tabby said...
It's a wreck because it's the ANTICHRIST in cupcake form! (And yes, tongue was firmly in cheek for that comment.)
- November 7, 2008 at 3:06 AM
I knew you'd have this featured, as soon as I saw it on the news!
Yum. Cake you can believe in. - November 7, 2008 at 4:43 AM
- Brenda said...
YAY!! Buffalo did something right ;)
This is an awesome creation. And I thought my cupcakes for our Daisy Scout meeting - done in a nice yellow frosting to match the petal we are working on - were creative LOL - November 7, 2008 at 7:07 AM
- KBK Bakery said...
Wow! That's a lot of cupcakes! When I first saw the picture I figured it was all M&M's! Well done them!
- November 7, 2008 at 7:18 AM
- jackie31337 said...
spackledorf said... our president-elect is delicious
I'm having weird cognitive crossover from passive-aggressive notes.com. You would have to add a 4-letter word to your comment for it to fit in over there, though. - November 7, 2008 at 7:18 AM
- heartafire said...
That zillycakes website is phenomonal---BEAUTIFUL cakes!
- November 7, 2008 at 7:41 AM
Congrats Zilly on such great work! Politics aside, that gal worked extremely hard to make not only all those cupcakes, but to set them up. I am in awe. And since I also live in the Elmwood Village, I cannot wait to order all my cakes from her. I love seeing a local business woman get some good press. Congratulations again, Zilly Cakes!
- November 7, 2008 at 8:14 AM
Not really an Obama supporter, but that is really cool. Can't imagine making that many cupcakes!
- November 7, 2008 at 8:43 AM
- Robin Brodeur said...
At first glance I thought they were Necco wafers on a cake...now it all makes sense!!!
- November 7, 2008 at 9:12 AM
And once again we prove: individual cupcakes... way cool; conjoined cupcakes... bad idea.
- November 7, 2008 at 9:41 AM
Is there any way to make that rich black frosting so it's not disgusting food coloring flavored? Or is that chocolate with some food color?
In any event, I'll take vanilla frosting anyday. - November 7, 2008 at 9:43 AM
- Landry said...
This is so cool! Definitely not a wreck.
- November 7, 2008 at 9:57 AM
- Unknown said...
Pixilation in CCC form! Magnificent.
~Amy B. - November 7, 2008 at 11:16 AM
- Rachel said...
If you want to know more about Zilly's process, I interviewed her yesterday about the Obama cupcake art at Cupcakes Take the Cake.
- November 7, 2008 at 1:37 PM
- Blythe said...
What's really funny is that my husband and I saw this on the news the other night and we both turned to each other and said.. "Now that is the world's largest CCC!!"
CRAAAZZY I tell ya! - November 7, 2008 at 2:14 PM
- jess said...
wow..the B-lo News didn't just report it..they featured it on the front page! I love that I heard about it on Cake Wrecks first though :)
- November 7, 2008 at 2:38 PM
- E.A.D. said...
Now that people, is how to do art with cupcakes! I just wish I could've been there to eat one! Yummy!
- November 8, 2008 at 12:01 AM
"And why is it always the snotty comments come from "anonymous?""
Valarie, you don't know the half of it. - November 8, 2008 at 7:32 AM
- Ms Unreliable said...
Love it, so amazing. I'm still waiting for the Sarah Palin CCC though, it's only a matter of time.
- November 8, 2008 at 8:55 AM
M&M's would have been much easier
- November 10, 2008 at 4:36 PM
AAAAAARRRRGGGG! Someone on Flickr just included me in their Cupcake Cake set of photos! I feel so misunderstood! What's a girl with cupcake integrity to do in such a situation?
Seriously, thanks for all of the comments above. I can't believe I didn't know about this blog before! I'll be sure to report on some of my own wrecks. Just stay tuned! - November 10, 2008 at 10:44 PM
As a baker, I can only praise Zilly and hope to god that we see more beautiful cupcake mosaics like this one, and less of those horrible.. HORRIBLE cupcake cakes. Seriously though Zilly, you did an amazing job! It reminds me of the baking version of pixel art!
- November 12, 2008 at 2:47 PM
- Brammy said...
Amazing, didnt realise it was cupcakes at first!
- November 12, 2008 at 8:50 PM
who gets to eat them?
- December 11, 2008 at 1:10 AM
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text:
can be set to make the plugin sensitive to what is in a topic, before allowing it to be edited. The comma separated list to fall back to text edit can include: html
- HTML tags (e.g.

, not including
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) or
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blocks (

... -->
= inline HTML Script tags - default
= inline Css style tags - default
= inline html tables (=
. TML tables are not excluded)
in WYSIWYG_EXCLUDE
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and WYSIWYG_EDITABLE_CALLS
in SitePreferences, or in WebPreferences for each web.
preference tells the translator
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It corresponds to div, span
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blocks, <literal>
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to tables and lists.
preference tells the translator
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=
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WYSIWYG editing, add table
to this list, and =
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automatically sticky.
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to stop the
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TML when certain specific attributes are present on the tag. This is most
useful when you have styling or alignment information in tags that must be
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on a tag, make it "stick" i.e. block conversion back to TML. For example, setting it toThis setting is used only after the page has been processed by the editor. If the editor does not support a particular tag or attribute and the editor corrupts the tag, this setting will not be helpful. It is only used to prevent an HTML tag from being converted back to TML. Format of the setting istable=background,lang;tr=valign
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* Set WYSIWYGPLUGIN_STICKYBITS = (?!IMG).*=id,lang,title,dir,on.*; A=accesskey,coords,shape,target; BDO=dir; BR=clear; COL=char,charoff,span,valign,width; COLGROUP=align,char,charoff,span,valign,width; DIR=compact; DIV=align,style; DL=compact; FONT=size,face; H[0-9]=align; HR=align,noshade,size,width; LEGEND=accesskey,align; LI=value; OL=compact,start,type; P=align; PARAM=name,type,value,valuetype; PRE=width; Q=cite; TABLE=align,bgcolor,.*?background-color:.*,frame,rules,summary,width; TBODY=align,char,charoff,valign; TD=abbr,align,axis,bgcolor,.*?background-color:.*,.*?border-color:.*,char,charoff,headers,height,nowrap,rowspan,scope,valign,width; TFOOT=align,char,charoff,valign; TH=abbr,align,axis,bgcolor,.*?background-color:.*,char,charoff,height,nowrap,rowspan,scope,valign,width,headers; THEAD=align,char,charoff,valign; TR=bgcolor,.*?background-color:.*,char,charoff,valign; UL=compact,typeIf you edit using the plain-text editor, you can use the <sticky>..</sticky> tags to delimit HTML (or TML) that you do not want to be WYSIWYG edited.
. It
specifies tags and their attributes that are to be ignored when making the
decision whether to keep the tag or not. For example, a
tag will normally be maintained in the TML. However setting
to font=face
will result in it being removed.
By default WYSIWYGPLUGIN_IGNOREATTRS
is empty. WYSIWYGPLUGIN_STICKYBITS
takes precedence over this setting.


text:
You're hanging out with a bunch of other mathematicians - you go out to dinner, you're on the train, you're at a department tea, et cetera. Someone says something like "A group of 100 people at a party are each receive hats with different prime numbers and ..." For the next few minutes everyone has fun solving the problem together.
I love puzzles like that. But there's a problem -- I running into the same puzzles over and over. But there must be lots of great problems I've never run into. So I'd like to hear problems that other people have enjoyed, and hopefully everyone will learn some new ones.
So: What are your favorite dinner conversation math puzzles?
I don't want to provide hard guidelines. But I'm generally interested in problems that are mathematical and not just logic puzzles. They shouldn't require written calculations or a convoluted answer. And they should be fun - with some sort of cute step, aha moment, or other satisfying twist. I'd prefer to keep things pretty elementary, but a cool problem requiring a little background is a-okay.
One problem per answer.
If you post the answer, please obfuscate it with something like rot13. Don't spoil the fun for everyone else.


text:
Simply enter the word you wish to find and the search engine will search for every instance of the word in the journals. For example: Fight. All instances of the use of the word fight will show up on the results page.
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Searches are not case sensitive. For example: george will come up with the same results as George.
Searching for a specific phrase may help narrow down the results. Rather long phrases are no problem. For example: "This white pudding we all esteem".
Because of the creative spellings used by the journalists, it may be necessary to try your search multiple times. For example: P?ro*. This search brings up numerous variant spellings of the French word pirogue, "a large dugout canoe or open boat." Searching for P?*r*og?* will bring up other variant spellings. Searching for canoe or boat also may be helpful.
Entering in only one field | Searches |
Year, Month, & Day | Single day |
Year & Month | Whole month |
Year | Whole year |
Month & Day | 1803-#-# to 1806-#-# |
Month | 1803-#-1 to 1806-#-31 |
Day | 1803-01-# to 1806-12-# |


text:
PayPal WPS ToolKit does not verify that the server hostname matches a domain name in the subjects Common Name (CN) or subjectAltName field of the X.509 certificate, which allows man-in-the-middle attackers to spoof SSL servers via an arbitrary valid certificate.
The product receives input or data, but it does not validate or incorrectly validates that the input has the properties that are required to process the data safely and correctly.
Name | Vendor | Start Version | End Version |
Wps_toolkit | Paypal | - (including) | - (including) |
Input validation is a frequently-used technique for checking potentially dangerous inputs in order to ensure that the inputs are safe for processing within the code, or when communicating with other components. When software does not validate input properly, an attacker is able to craft the input in a form that is not expected by the rest of the application. This will lead to parts of the system receiving unintended input, which may result in altered control flow, arbitrary control of a resource, or arbitrary code execution. Input validation is not the only technique for processing input, however. Other techniques attempt to transform potentially-dangerous input into something safe, such as filtering (CWE-790) - which attempts to remove dangerous inputs - or encoding/escaping (CWE-116), which attempts to ensure that the input is not misinterpreted when it is included in output to another component. Other techniques exist as well (see CWE-138 for more examples.) Input validation can be applied to:
Data can be simple or structured. Structured data can be composed of many nested layers, composed of combinations of metadata and raw data, with other simple or structured data. Many properties of raw data or metadata may need to be validated upon entry into the code, such as:
Implied or derived properties of data must often be calculated or inferred by the code itself. Errors in deriving properties may be considered a contributing factor to improper input validation.
Note that "input validation" has very different meanings to different people, or within different classification schemes. Caution must be used when referencing this CWE entry or mapping to it. For example, some weaknesses might involve inadvertently giving control to an attacker over an input when they should not be able to provide an input at all, but sometimes this is referred to as input validation. Finally, it is important to emphasize that the distinctions between input validation and output escaping are often blurred, and developers must be careful to understand the difference, including how input validation is not always sufficient to prevent vulnerabilities, especially when less stringent data types must be supported, such as free-form text. Consider a SQL injection scenario in which a person's last name is inserted into a query. The name "O'Reilly" would likely pass the validation step since it is a common last name in the English language. However, this valid name cannot be directly inserted into the database because it contains the "'" apostrophe character, which would need to be escaped or otherwise transformed. In this case, removing the apostrophe might reduce the risk of SQL injection, but it would produce incorrect behavior because the wrong name would be recorded.


text: Please enter your valid username (or email address) and you will be sent a link to reset your password. You must use the same username you have registered with us. If you have forgotten your username or you no longer have the same email address then you must contact us directly with proof of your identity.


text:
PC-SPES (PDQ®)–Health Professional Version
NOTE: There is either no new research on this topic or the recent published research is weak and not appropriate for inclusion in the summary. Therefore, the information in this summary is no longer being updated and is provided for reference purposes only.
This cancer information summary provides an overview of the use of PC-SPES as a treatment in people with cancer. The summary includes a brief history of PC-SPES research, the results of clinical trials, and possible adverse effects of PC-SPES. Included in this summary is a discussion of the contamination of PC-SPES and its withdrawal from avenues of distribution.
This summary contains the following key information:
- PC-SPES is a patented mixture of eight herbs.
- PC-SPES was sold as a dietary supplement to support and promote healthy prostate function.
- Each herb used in PC-SPES has been reported to have anti-inflammatory, antioxidant, or anticarcinogenic properties.
- PC-SPES was recalled and withdrawn from the market because certain batches were contaminated with Food and Drug Administration–controlled prescription drugs.
- The manufacturer is no longer in operation, and PC-SPES is no longer being made.
- There is evidence from both laboratory and animal studies to suggest that PC-SPES had some effect in inhibiting prostate cancer cell growth and prostate-specific antigen (PSA) expression, but it is not known whether these results were caused by adulterants such as diethylstilbestrol, which is an estrogenic compound, the herbs in PC-SPES, or their combination.
- Evidence from clinical trials has shown that PC-SPES lowers PSA and testosterone levels in humans, but it is not known whether these results were caused by adulterants, the herbs in PC-SPES, or their combination.
- There is some evidence to suggest that PC-SPES has some anticancer effects that are not related to estrogen-like activity.
- Although there are products that claim to be substitutes for PC-SPES, they are not the patented original formulation. Few of these products have been the subject of laboratory or clinical trials reported in the peer-reviewed medical literature.
General Information
Note: Separate PDQ summaries on Prostate Cancer, Nutrition, and Dietary Supplements and Prostate Cancer Treatment are also available.
PC-SPES is a patented herbal mixture that was sold as a dietary supplement and used as a complementary and alternative medicine (CAM) treatment for prostate cancer. It is a combination of the following eight herbs:
- Baikal skullcap (Scutellaria baicalensis Georgi).
- Chrysanthemum (Dendranthema morifolium [Ramat.] Tzvelev [synonym Chrysanthemum morifolium]).
- Ganoderma (Ganoderma lucidum [Curtis:fr] Karst.).
- Isatis (Isatis indigotica Fort.).
- Licorice (Glycyrrhiza glabra L. or Glycyrrhiza uralensis Fisch. ex DC.).
- Panax ginseng C.A. Meyer or pseudoginseng (Panax pseudoginseng var. notoginseng Hoo & tseng [synonym Panax notoginseng (Burkill)] F.H.Chen).
- Isodon rubescens (Hemsl.) Hara (synonym Rabdosia rubescens [Hemsl.] Hara).
- Saw palmetto (Serenoa repens [Bartr.] Small).
With the exception of saw palmetto, the herbs in PC-SPES have been used individually or in combination in Traditional Chinese Medicine (TCM) for a variety of health problems, including those of the prostate, for hundreds of years.[1,2]
PC-SPES is an herbal product that resulted from a collaboration between a chemist at the New York Medical College in Valhalla, New York, and a Chinese herbalist and doctor of TCM in China. Their idea was to combine TCM with the scientific techniques of Western laboratory research. In the United States, a series of in vitro and in vivo laboratory studies was started on the mixture of herbs used in TCM specially formulated to treat prostate problems. Researchers published the results of these studies, which showed promising anticancer activity from PC-SPES.[3-11]
Considerable research has been conducted on the anticancer properties of the eight individual botanicals in PC-SPES.
Baikal skullcap (Scutellaria baicalensis)—Chinese name huang qin—contains baicalin and wogonin, two active flavones. Baicalin converts to baicalein, which is another active flavone. In vitro, baicalin and baicalein inhibit cell growth of AD LNCaP and JCA-1 AI human prostate cancer cell lines,[12,13] as well as inducing apoptosis in human LNCaP cells.[14] Baicalin also shows antimutagenic and antioxidant activity in vitro as well as free radical scavenging ability.[15-20]
Licorice (Glycyrrhiza glabra or Glycyrrhiza uralensis)—Chinese name gan cao—contains the very active flavonoid licochalcone A, which has demonstrated in vitro estrogenic activity.[21] This botanical shows a broad range of anticancer activity in vitro. It enhances the cytotoxicity of commonly used anticancer drugs and induces apoptosis in MCF-7 human breast cancer and HL-60 promyelocytic leukemia cell lines.[21-24]
Reishi mushroom (Ganoderma lucidum [Curtis: fr.] Karst.)—Chinese name ling zhi— has been shown to aid in the recovery of leukocyte counts in irradiated mice in a dose-dependent manner. It contains the polysaccharide G009, which has demonstrated antioxidant behavior against HL-60 cells in vitro and dose-dependent inhibition of lipid peroxidation in rat brain cells in vitro.[25-29]
Isatis (Isatis indigotica)—Chinese name da qing ve—contains active agents in each part of the plant.[2] TCM has different names for the medicinals coming from the leaf, stem, and root and uses these plant products for different purposes. Indirubin, an active ingredient, and its analogs have demonstrated inhibition of cyclin-dependent kinases in human mammary carcinoma cell line MCF-7 in vitro.[30]
Ginseng (Panax ginseng or Panax pseudoginseng var. notoginseng)—Chinese name tianqi—contains ginsenosides and saponins. Of the 30 ginsenosides that have been isolated from Panax ginseng, only the 20(S)-protopanaxadiol type R3 has inhibited cell growth and suppressed PSA expression, androgen receptor and 5-alpha-reductase activity, and PCNA production in vitro.[31-33]
Chrysanthemum flowers (Dendranthema morifolium)—Chinese name ju hua—contain triterpene diols and triols. Arnidiol exhibited cytotoxicity in vitro against 58 of the 60 human cancer cell lines developed by the National Cancer Institute (NCI) Developmental Therapeutics Program.[34]
The botanical rabdosia rubescens (Isodon rubescens)—Chinese name dong ling cao—has two very active agents, oridonin and rubesencin b. Oridonin inhibits DNA synthesis in vitro,[1] and rubesencin b inhibited cell growth in cancer cell lines in vitro and in a mouse model.[35]
Saw palmetto (Serenoa repens) is the only botanical in PC-SPES that is not used in TCM. There is strong evidence from human trials that saw palmetto has some activity against benign prostatic hypertrophy (BPH), including improved urine flow and less erectile dysfunction when compared with placebo or finasteride. S. repens also exhibits antiestrogenic activity in placebo-controlled BPH trials. In LNCaP cells, S. repens produced apoptosis in vitro.[36-40]
Exactly how PC-SPES works in the body is still unknown. The presence of adulterants and varying amounts of the active agents in each lot of PC-SPES complicates the interpretation of any results from studies that might lead to an explanation of its mechanisms of action. More studies of the individual components of the mixture and testing of a standard formulation that is free of adulterants are needed before any conclusions can be reached about the level of cytotoxicity, antineoplasticity, or estrogenicity of PC-SPES.
The National Center for Complementary and Integrative Health (NCCIH) stopped funding to studies of PC-SPES after the drug contamination was detected and made public, although the laboratory studies were later resumed.
Although manufacturers are selling supplements purporting to be substitutes, the only company that had a license from the patent holder to manufacture PC-SPES is no longer in business, and the product cannot be legally manufactured in the United States without the patent holder's permission. PC-SPES is not legally available in the United States.
- Huang KC, Williams WM: The Pharmacology of Chinese Herbs. 2nd ed. CRC Press, 1998.
- Zhu YP: Chinese Materia Medica: Chemistry, Pharmacology, and Applications. Harwood Academic, 1998.
- Halicka HD, Ardelt B, Juan G, et al.: Apoptosis and cell cycle effects induced by extracts of the Chinese herbal preparation PC SPES. Int J Oncol 11: 437-48, 1997.
- Hsieh T, Chen SS, Wang X, et al.: Regulation of androgen receptor (AR) and prostate specific antigen (PSA) expression in the androgen-responsive human prostate LNCaP cells by ethanolic extracts of the Chinese herbal preparation, PC-SPES. Biochem Mol Biol Int 42 (3): 535-44, 1997. [PUBMED Abstract]
- Chenn S: In vitro mechanism of PC SPES. Urology 58 (2 Suppl 1): 28-35; discussion 38, 2001. [PUBMED Abstract]
- Hsieh TC, Wu JM: Mechanism of action of herbal supplement PC-SPES: elucidation of effects of individual herbs of PC-SPES on proliferation and prostate specific gene expression in androgen-dependent LNCaP cells. Int J Oncol 20 (3): 583-8, 2002. [PUBMED Abstract]
- Chen S, Ruan Q, Bedner E, et al.: Effects of the flavonoid baicalin and its metabolite baicalein on androgen receptor expression, cell cycle progression and apoptosis of prostate cancer cell lines. Cell Prolif 34 (5): 293-304, 2001. [PUBMED Abstract]
- Kubota T, Hisatake J, Hisatake Y, et al.: PC-SPES: a unique inhibitor of proliferation of prostate cancer cells in vitro and in vivo . Prostate 42 (3): 163-71, 2000. [PUBMED Abstract]
- Darzynkiewicz Z, Traganos F, Wu JM, et al.: Chinese herbal mixture PC SPES in treatment of prostate cancer (review). Int J Oncol 17 (4): 729-36, 2000. [PUBMED Abstract]
- Marks LS, DiPaola RS, Nelson P, et al.: PC-SPES: herbal formulation for prostate cancer. Urology 60 (3): 369-75; discussion 376-7, 2002. [PUBMED Abstract]
- Pirani JF: The effects of phytotherapeutic agents on prostate cancer: an overview of recent clinical trials of PC SPES. Urology 58 (2 Suppl 1): 36-8, 2001. [PUBMED Abstract]
- Huerta S, Arteaga JR, Irwin RW, et al.: PC-SPES inhibits colon cancer growth in vitro and in vivo. Cancer Res 62 (18): 5204-9, 2002. [PUBMED Abstract]
- Schwarz RE, Donohue CA, Sadava D, et al.: Pancreatic cancer in vitro toxicity mediated by Chinese herbs SPES and PC-SPES: implications for monotherapy and combination treatment. Cancer Lett 189 (1): 59-68, 2003. [PUBMED Abstract]
- Chan FL, Choi HL, Chen ZY, et al.: Induction of apoptosis in prostate cancer cell lines by a flavonoid, baicalin. Cancer Lett 160 (2): 219-28, 2000. [PUBMED Abstract]
- Okita K, Li Q, Murakamio T, et al.: Anti-growth effects with components of Sho-saiko-to (TJ-9) on cultured human hepatoma cells. Eur J Cancer Prev 2 (2): 169-75, 1993. [PUBMED Abstract]
- Matsuzaki Y, Kurokawa N, Terai S, et al.: Cell death induced by baicalein in human hepatocellular carcinoma cell lines. Jpn J Cancer Res 87 (2): 170-7, 1996. [PUBMED Abstract]
- Kimura Y, Matsushita N, Okuda H: Effects of baicalein isolated from Scutellaria baicalensis on interleukin 1 beta- and tumor necrosis factor alpha-induced adhesion molecule expression in cultured human umbilical vein endothelial cells. J Ethnopharmacol 57 (1): 63-7, 1997. [PUBMED Abstract]
- Hsieh TC, Lu X, Chea J, et al.: Prevention and management of prostate cancer using PC-SPES: a scientific perspective. J Nutr 132 (11 Suppl): 3513S-3517S, 2002. [PUBMED Abstract]
- Ikezoe T, Chen SS, Heber D, et al.: Baicalin is a major component of PC-SPES which inhibits the proliferation of human cancer cells via apoptosis and cell cycle arrest. Prostate 49 (4): 285-92, 2001. [PUBMED Abstract]
- Hsu SL, Hsieh YC, Hsieh WC, et al.: Baicalein induces a dual growth arrest by modulating multiple cell cycle regulatory molecules. Eur J Pharmacol 425 (3): 165-71, 2001. [PUBMED Abstract]
- Gao Z, Huang K, Yang X, et al.: Free radical scavenging and antioxidant activities of flavonoids extracted from the radix of Scutellaria baicalensis Georgi. Biochim Biophys Acta 1472 (3): 643-50, 1999. [PUBMED Abstract]
- Armanini D, Bonanni G, Palermo M: Reduction of serum testosterone in men by licorice. N Engl J Med 341 (15): 1158, 1999. [PUBMED Abstract]
- Rafi MM, Vastano BC, Zhu N, et al.: Novel polyphenol molecule isolated from licorice root (Glycrrhiza glabra) induces apoptosis, G2/M cell cycle arrest, and Bcl-2 phosphorylation in tumor cell lines. J Agric Food Chem 50 (4): 677-84, 2002. [PUBMED Abstract]
- Rafi MM, Rosen RT, Vassil A, et al.: Modulation of bcl-2 and cytotoxicity by licochalcone-A, a novel estrogenic flavonoid. Anticancer Res 20 (4): 2653-8, 2000 Jul-Aug. [PUBMED Abstract]
- Wang ZY, Nixon DW: Licorice and cancer. Nutr Cancer 39 (1): 1-11, 2001. [PUBMED Abstract]
- Bao XF, Wang XS, Dong Q, et al.: Structural features of immunologically active polysaccharides from Ganoderma lucidum. Phytochemistry 59 (2): 175-81, 2002. [PUBMED Abstract]
- Chen WC, Hau DM, Lee SS: Effects of Ganoderma lucidum and krestin on cellular immunocompetence in gamma-ray-irradiated mice. Am J Chin Med 23 (1): 71-80, 1995. [PUBMED Abstract]
- Hsu HY, Lian SL, Lin CC: Radioprotective effect of Ganoderma lucidum (Leyss. ex. Fr.) Karst after X-ray irradiation in mice. Am J Chin Med 18 (1-2): 61-9, 1990. [PUBMED Abstract]
- Lee JM, Kwon H, Jeong H, et al.: Inhibition of lipid peroxidation and oxidative DNA damage by Ganoderma lucidum. Phytother Res 15 (3): 245-9, 2001. [PUBMED Abstract]
- Marko D, Schätzle S, Friedel A, et al.: Inhibition of cyclin-dependent kinase 1 (CDK1) by indirubin derivatives in human tumour cells. Br J Cancer 84 (2): 283-9, 2001. [PUBMED Abstract]
- Liu WK, Xu SX, Che CT: Anti-proliferative effect of ginseng saponins on human prostate cancer cell line. Life Sci 67 (11): 1297-306, 2000. [PUBMED Abstract]
- Yun TK, Lee YS, Lee YH, et al.: Anticarcinogenic effect of Panax ginseng C.A. Meyer and identification of active compounds. J Korean Med Sci 16 (Suppl): S6-18, 2001. [PUBMED Abstract]
- Surh YJ, Na HK, Lee JY, et al.: Molecular mechanisms underlying anti-tumor promoting activities of heat-processed Panax ginseng C.A. Meyer. J Korean Med Sci 16 (Suppl): S38-41, 2001. [PUBMED Abstract]
- Ukiya M, Akihisa T, Tokuda H, et al.: Constituents of Compositae plants III. Anti-tumor promoting effects and cytotoxic activity against human cancer cell lines of triterpene diols and triols from edible chrysanthemum flowers. Cancer Lett 177 (1): 7-12, 2002. [PUBMED Abstract]
- Jing JY, Reed E: Preliminary study of the effect of selected Chinese natural drugs on human ovarian cancer cells. Oncol Rep 2: 571-5, 1995.
- Marks LS, Hess DL, Dorey FJ, et al.: Tissue effects of saw palmetto and finasteride: use of biopsy cores for in situ quantification of prostatic androgens. Urology 57 (5): 999-1005, 2001. [PUBMED Abstract]
- Di Silverio F, D'Eramo G, Lubrano C, et al.: Evidence that Serenoa repens extract displays an antiestrogenic activity in prostatic tissue of benign prostatic hypertrophy patients. Eur Urol 21 (4): 309-14, 1992. [PUBMED Abstract]
- Di Silverio F, Monti S, Sciarra A, et al.: Effects of long-term treatment with Serenoa repens (Permixon) on the concentrations and regional distribution of androgens and epidermal growth factor in benign prostatic hyperplasia. Prostate 37 (2): 77-83, 1998. [PUBMED Abstract]
- Iguchi K, Okumura N, Usui S, et al.: Myristoleic acid, a cytotoxic component in the extract from Serenoa repens, induces apoptosis and necrosis in human prostatic LNCaP cells. Prostate 47 (1): 59-65, 2001. [PUBMED Abstract]
- Wilt T, Ishani A, Mac Donald R: Serenoa repens for benign prostatic hyperplasia. Cochrane Database Syst Rev (3): CD001423, 2002. [PUBMED Abstract]
In 1997, the herbal formula for PC-SPES was patented in the United States.[1] A company, BotanicLab (Brea, California), was formed to produce, distribute, and sell the product. PC-SPES was sold through the BotanicLab website (the website was taken down after PC-SPES was recalled) and through selected distributors. Anecdotal information about the product and its positive effects was widely circulated on the Internet through websites that informed prostate cancer patients about new developments in treatment. At the same time, the published papers were being read by the scientific community, and the findings were presented at various conferences. As a result, clinicians and researchers began looking at PC-SPES as one of the first viable treatments to come out of the alternative medicine community.
The manufacturing process for PC-SPES has been described by the manufacturer as follows: extracts of raw plant material were obtained from the specified plants, which were grown in particular geographic regions in China and harvested at certain times of the year to reduce the natural variation inherent in any biological product. The extracts were shipped to the United States, where high-performance liquid chromatography (HPLC) was used to monitor the key active compounds—which are believed to be directly related to the clinical effects—for batch-to-batch reproducibility. Activity-related biomarkers were kept in a constant concentration from lot to lot. A commercial testing laboratory (Truesdail Laboratory; Tustin, California) was used to guarantee that each batch was free from contamination with heavy metals, pesticides, microorganisms and products, and prescription drugs. Each lot was standardized by an anticancer bioassay for an effective dose of 50% in vitro inhibition of cell growth using human LNCaP cells for androgen-dependent (AD) prostate cancer and DU-145 cells for androgen-independent (AI) prostate cancer. The powder was then encapsulated, bottled, labeled, and sterilized at the BotanicLab facility.[2]
In 2001, allegations that PC-SPES contained the synthetic estrogen diethylstilbestrol (DES) started to appear on e-mail listservs used by prostate cancer patients and in online newsletters. Prostate cancer patients who were taking PC-SPES noticed that their recent medication was not as effective as the previous batches.[3] A sample of PC-SPES submitted to a testing laboratory by BotanicLab in August 2001 found no DES. BotanicLab posted the letter from the laboratory on their website, claiming that PC-SPES contained no DES. However, in other tests of six different lots of PC-SPES received from two different sources in August 2001, Rocky Mountain Instrumental Laboratory found varying amounts of DES in three lots. More tests done by the California Department of Health Services in February 2002 did not find DES but did find warfarin, a prescription drug used as a blood thinner.[4]
The presence of a synthetic estrogen such as DES was suspected early in the clinical use of PC-SPES after reports in the literature discussed the mixture's estrogen-like ability to lower prostate-specific antigen (PSA) levels in AD prostate cancer patients. In addition, the side effects of treatment were similar to those of estrogen therapy. [5-7] In one study, patients who showed the most response to PC-SPES were also those who were the most responsive to DES.[8,9] The same study also attempted to find out whether DES or similar compounds were present in PC-SPES. Transcriptional activation assays in yeast strain PL3 Saccharomyces cerevisiae using an ethanolic extract of PC-SPES showed estrogenic activity similar to 1nM estradiol. In addition, ovariectomized CD-1 mice showed substantially increased uterine weights. HPLC, gas chromatography, and mass spectrometry did not reveal the presence of DES but rather that of a compound with similar chemical characteristics. The authors of the report concluded that PC-SPES contains estrogenic compounds that are distinct from DES or other synthetic estrogens.[9]
A definitive evaluation of PC-SPES analyzed specific lots of PC-SPES capsules manufactured from 1996 to 2001.[10] In addition to using HPLC to isolate, identify, and quantify the synthetic drugs and active phytoestrogens, this study also identified components using proton nuclear magnetic resonance, gas chromatography/mass spectrometry, and mass spectra analysis. Tests showed the presence of the synthetic drugs indomethacin (a nonsteroidal anti-inflammatory drug not previously reported in the literature or found in other testing), DES, and warfarin. Testing was also done for concentrations of the two naturally occurring phytosterols, licochalcone A and baicalin. Test results indicated a history of rising and falling levels of contamination by the three synthetic drugs and a recent rise in the naturally occurring phytochemicals in PC-SPES. Lots of PC-SPES manufactured in 1996 through mid-1999 contained indomethacin ranging from 1.07 mg/g to 13.19 mg/g and DES ranging from 107.28 µg/g to 159.27 µg/g and were 2 to 6 times more antineoplastic and up to 50 times more estrogenic than lots manufactured after the spring of 1999. In vitro testing of ethanolic extracts of PC-SPES against LNCaP, PC-3, and DU-145 prostate cancer cell lines showed a decrease in both antineoplasticity and estrogenicity in lots of PC-SPES manufactured in June 1998 through August 2001, which correlated with the amount of DES and indomethacin contamination.[10] Another in vitro test of suspected lots of PC-SPES manufactured from 2000 to 2001 also showed the presence of DES.[11]
Although the laboratory testing showed that certain lots of the mixture contained indomethacin, warfarin, and DES, the amount of DES present may not have accounted for all of the estrogenic effect of PC-SPES. There is some evidence that the mixture acts differently from DES at the molecular level.[12,13] In addition, its anticancer effects on both AI prostate cancer and AD prostate cancer may point to a mechanism other than estrogen-like activity.[10,14,15] The in vitro activity of PC-SPES against cancer cells other than prostate also gives rise to the speculation that its estrogen-like qualities might not account for all of the mixture's anticancer activity.[16,17]
- Chen S, Wang X: Herbal Composition for Treating Prostate Carcinoma. US Patent 5665393. September 9, 1997. Washington, DC: US Patent and Trademark Office, 1997. Available online. Last accessed April 12, 2016.
- Marks LS, DiPaola RS, Nelson P, et al.: PC-SPES: herbal formulation for prostate cancer. Urology 60 (3): 369-75; discussion 376-7, 2002. [PUBMED Abstract]
- PSA Rising: Prostate Cancer Survivor News, Info and Support. New York, NY: PSA Rising, 2005. Available online. Last accessed April 12, 2016.
- Ko R, Wilson RD, Loscutoff S: PC-SPES. Urology 61 (6): 1292, 2003. [PUBMED Abstract]
- Oh WK, George DJ, Hackmann K, et al.: Activity of the herbal combination, PC-SPES, in the treatment of patients with androgen-independent prostate cancer. Urology 57 (1): 122-6, 2001. [PUBMED Abstract]
- Oh WK, George DJ, Kantoff PW: Rapid rise of serum prostate specific antigen levels after discontinuation of the herbal therapy PC-SPES in patients with advanced prostate carcinoma: report of four cases. Cancer 94 (3): 686-9, 2002. [PUBMED Abstract]
- de la Taille A, Hayek OR, Burchardt M, et al.: Role of herbal compounds (PC-SPES) in hormone-refractory prostate cancer: two case reports. J Altern Complement Med 6 (5): 449-51, 2000. [PUBMED Abstract]
- Pirani JF: The effects of phytotherapeutic agents on prostate cancer: an overview of recent clinical trials of PC SPES. Urology 58 (2 Suppl 1): 36-8, 2001. [PUBMED Abstract]
- DiPaola RS, Zhang H, Lambert GH, et al.: Clinical and biologic activity of an estrogenic herbal combination (PC-SPES) in prostate cancer. N Engl J Med 339 (12): 785-91, 1998. [PUBMED Abstract]
- Sovak M, Seligson AL, Konas M, et al.: Herbal composition PC-SPES for management of prostate cancer: identification of active principles. J Natl Cancer Inst 94 (17): 1275-81, 2002. [PUBMED Abstract]
- Guns ES, Goldenberg SL, Brown PN: Mass spectral analysis of PC-SPES confirms the presence of diethylstilbestrol. Can J Urol 9 (6): 1684-8; discussion 1689, 2002. [PUBMED Abstract]
- Chen S, Ruan Q, Bedner E, et al.: Effects of the flavonoid baicalin and its metabolite baicalein on androgen receptor expression, cell cycle progression and apoptosis of prostate cancer cell lines. Cell Prolif 34 (5): 293-304, 2001. [PUBMED Abstract]
- Bonham M, Arnold H, Montgomery B, et al.: Molecular effects of the herbal compound PC-SPES: identification of activity pathways in prostate carcinoma. Cancer Res 62 (14): 3920-4, 2002. [PUBMED Abstract]
- Reynolds T: Contamination of PC-SPES remains a mystery. J Natl Cancer Inst 94 (17): 1266-8, 2002. [PUBMED Abstract]
- Malkowicz SB: The role of diethylstilbestrol in the treatment of prostate cancer. Urology 58 (2 Suppl 1): 108-13, 2001. [PUBMED Abstract]
- Huerta S, Arteaga JR, Irwin RW, et al.: PC-SPES inhibits colon cancer growth in vitro and in vivo. Cancer Res 62 (18): 5204-9, 2002. [PUBMED Abstract]
- Schwarz RE, Donohue CA, Sadava D, et al.: Pancreatic cancer in vitro toxicity mediated by Chinese herbs SPES and PC-SPES: implications for monotherapy and combination treatment. Cancer Lett 189 (1): 59-68, 2003. [PUBMED Abstract]
Laboratory/Animal/Preclinical Studies
Before the discovery of diethylstilbestrol (DES), warfarin, and indomethacin contamination, PC-SPES appeared to have some efficacy as an antineoplastic agent in laboratory and animal studies. These studies are presented below. Due to the fact that there was no standardization of the composition of PC-SPES or any knowledge of the amount of contamination of each lot used in testing, it is difficult to interpret the data from these studies.
In one study that attempted to measure the effects of the whole PC-SPES mixture versus that of individual herbs of PC-SPES on prostate-specific antigen (PSA) expression and cell growth, LNCaP cells were treated with ethanol extracts of PC-SPES and each of the eight herbs. The PC-SPES mixture reduced cell growth by 72% to 80%, while Dendranthema morifolium (Ramat.) Tzvelev (synonym Chrysanthemum morifolium) (chrysanthemum) produced the highest reduction of the herb group at 85%. Panax pseudoginseng var. notoginseng Hoo & tseng (Synonym Panax notoginseng [Burkill] F.H.Chen) was next at 80.9% reduction, followed by Glycyrrhiza uralensis Fisch ex DC. (73%). The lowest reduction in cell growth was exhibited by Serenoa repens (Bartr.) Small (14.5%). Scutellaria baicalensis Georgi, Serenoa repens, and Glycyrrhiza uralensis lowered PSA expression, but each of the other herbs increased PSA expression. The ability of individual herbs to reduce PSA expression was not uniform, but the PC-SPES mixture as a whole exhibited a uniform response. The varying results with the individual herbs and the positive response of the cells (i.e., increased cytotoxicity and reduced PSA expression) to the aggregate PC-SPES mixture may suggest that the botanicals in PC-SPES work in concert and that no individual herb can account for the overall effects of the mixture.[1]
In other studies, PC-SPES was found to inhibit clonal growth in three human prostate cancer cell lines: LNCaP, PC-3, and DU-145. Cell cycle analysis showed cell cycle arrest at the G2 phase.[2] Cell proliferation and reduced clonogenicity were observed in cancer cell lines other than those of prostate cancer: human breast carcinoma lines MCF-7 and T47-D, SK-N-MC neuroepithelioma, COLO 38 melanoma, U937 histiomonocytic lymphoma, and HL-60 and MOLT-4 leukemias. Cytotoxic and cytostatic effects of PC-SPES were common to all tumor cell lines tested.[3]
In another study evaluating regulation of PSA expression and androgen receptor (AR) activity, LNCaP prostate cancer cell lines showed downregulation of both proliferating cell nuclear antigen (PCNA) and PSA expression. PSA changes occurred concurrently with the decrease of PCNA. The results suggest that PC-SPES modulates cell growth by changing PCNA expression and may decrease PSA levels indirectly by suppressing AR expression.[4]
None of the studies above indicated lot number or year of manufacture of the PC-SPES used. Therefore, it is not possible to assess the amount of contamination of the mixtures used in the studies or whether the mixtures used were not in fact contaminated.
A 1998 study that evaluated estrogenic activity of extracts of PC-SPES, ginseng (Panax ginseng C.A. Meyer), saw palmetto, DES, and estrone (estradiol-17 beta) in vitro reported on the estrogenic response of ovariectomized CD-1 mice to PC-SPES extract as well as the response to PC-SPES capsules in eight prostate cancer patients who had received previous therapy. [5] This study used four samples of PC-SPES ordered in separate purchases from BotanicLab. No lot numbers were supplied in the study. Lot numbers from October 1996 through July 1998 were later tested for contamination and had DES levels of 114.74 μg/g to 159.27 μg/g, as well as the highest detected levels of indomethacin of the PC-SPES lots tested.[6] In vitro tests of PC-SPES extract or estradiol showed estrogenic activity similar to 1 nM estradiol on estrogen receptor Y253 yeast strain. Transcriptional activation assays in yeast strain PL3 Saccharomyces cerevisiae with ethanolic extract of PC-SPES exhibited estrogen-like effects. In the eight prostate cancer patients, serum testosterone concentrations decreased during the use of PC-SPES and increased within 3 weeks after treatment was discontinued. PSA levels decreased in all eight patients. Side effects in all eight patients were similar to those seen after treatment with estrogen: breast tenderness and loss of libido. One patient had superficial venous thrombosis. In addition to baicalin, two other compounds purified from PC-SPES, isoliquiritigenin and wogonin, have been shown to reduce PSA levels and downregulate AR.[7]
By incorporating PC-SPES into the rat diet, researchers conducting an in vivo study showed antitumor effects using a Dunning R3327 rat prostate cancer model. Levels of 0.05% and 0.025% of dietary PC-SPES were fed to the rats over a 6-week period. No toxicity was seen, nor was there a difference in the food intake of the rats during this time. Pulmonary tumors were induced by intradermal injections of MAT-LyLu cells, which are particularly resistant to many forms of treatment. Tumor incidence was inhibited in a dose-dependent manner, and the rate of tumor growth showed the same dose-dependent response.[8,9]
In another study, which used male BNX nu/nu immunodeficient nude mice, PC-SPES was also administered orally, but in suspension. The mice received 300 rad of whole-body irradiation, after which they were inoculated with either PC-3 or DU-145 prostate cancer cell lines. Treatment with PC-SPES began the day after injection. Results showed that PC-SPES suppressed the growth of DU-145 tumors compared with tumor growth in the control group. Cytological analysis showed apoptosis in the treated group that was not apparent in the control group.[10]
In two other studies, clinical studies of patients were initiated along with in vitro and in vivo research. The results of these two patient groups are discussed in the Human/Clinical Trials section of this summary. The first study, preceding more extensive research, examined in vitro activity of PC-SPES against LNCaP, LNCaP-bcl-2, PC-3, and DU-145 cells lines. Results showed that PC-SPES was active in suppressing both hormone-sensitive and hormone-insensitive prostate cancer cell lines. In the subsequent study, research was conducted in vitro on the ability of PC-SPES to induce apoptosis in androgen-independent (AI) prostate cancer cell lines, and in vivo on the effect of oral PC-SPES on the growth of xenografted PC-3 tumors in immunodeficient male mice. Mice in the treatment arm—in which treatment was started 1 week after implantation—showed a significant decrease in tumor weight when compared with mice in the control arm. PC-SPES showed activity against both androgen-sensitive and AI prostate cancer in the patients and suppressed tumor growth in AI tumors in mice.[10-12] In both studies, the patients were given capsules manufactured between 1996 and 1999, a time when contamination levels of DES were highest.[6]
Another study in rats demonstrated that PC-SPES (one lot contaminated with DES and one lot without DES) caused some decrease in the activity of a liver enzyme involved in drug metabolism (CYP3A).[13]
- Hsieh TC, Lu X, Chea J, et al.: Prevention and management of prostate cancer using PC-SPES: a scientific perspective. J Nutr 132 (11 Suppl): 3513S-3517S, 2002. [PUBMED Abstract]
- Kubota T, Hisatake J, Hisatake Y, et al.: PC-SPES: a unique inhibitor of proliferation of prostate cancer cells in vitro and in vivo . Prostate 42 (3): 163-71, 2000. [PUBMED Abstract]
- Ko R, Wilson RD, Loscutoff S: PC-SPES. Urology 61 (6): 1292, 2003. [PUBMED Abstract]
- Hsieh TC, Wu JM: Mechanism of action of herbal supplement PC-SPES: elucidation of effects of individual herbs of PC-SPES on proliferation and prostate specific gene expression in androgen-dependent LNCaP cells. Int J Oncol 20 (3): 583-8, 2002. [PUBMED Abstract]
- DiPaola RS, Zhang H, Lambert GH, et al.: Clinical and biologic activity of an estrogenic herbal combination (PC-SPES) in prostate cancer. N Engl J Med 339 (12): 785-91, 1998. [PUBMED Abstract]
- Sovak M, Seligson AL, Konas M, et al.: Herbal composition PC-SPES for management of prostate cancer: identification of active principles. J Natl Cancer Inst 94 (17): 1275-81, 2002. [PUBMED Abstract]
- Chen S, Gao J, Halicka HD, et al.: Down-regulation of androgen-receptor and PSA by phytochemicals. Int J Oncol 32 (2): 405-11, 2008. [PUBMED Abstract]
- Tiwari RK, Geliebter J, Garikapaty VP, et al.: Anti-tumor effects of PC-SPES, an herbal formulation in prostate cancer. Int J Oncol 14 (4): 713-9, 1999. [PUBMED Abstract]
- Geliebter J, Mittelman A, Tiwari RK: PC-SPES and prostate cancer. J Nutr 131 (1): 164S-166S, 2001. [PUBMED Abstract]
- de la Taille A, Buttyan R, Hayek O, et al.: Herbal therapy PC-SPES: in vitro effects and evaluation of its efficacy in 69 patients with prostate cancer. J Urol 164 (4): 1229-34, 2000. [PUBMED Abstract]
- Pirani JF: The effects of phytotherapeutic agents on prostate cancer: an overview of recent clinical trials of PC SPES. Urology 58 (2 Suppl 1): 36-8, 2001. [PUBMED Abstract]
- de la Taille A, Hayek OR, Buttyan R, et al.: Effects of a phytotherapeutic agent, PC-SPES, on prostate cancer: a preliminary investigation on human cell lines and patients. BJU Int 84 (7): 845-50, 1999. [PUBMED Abstract]
- Wadsworth T, Poonyagariyagorn H, Sullivan E, et al.: In vivo effect of PC-SPES on prostate growth and hepatic CYP3A expression in rats. J Pharmacol Exp Ther 306 (1): 187-94, 2003. [PUBMED Abstract]
Human/Clinical Studies
One published randomized cross-over study of patients with androgen-independent (AI) prostate cancer who initially received either 960 mg of PC-SPES 3 times a day or 3 mg of diethylstilbestrol (DES) once a day before crossing over to the other regimen; when disease progression occurred, there were reports of data demonstrating the presence and levels of adulterants in the four lots of PC-SPES used in this trial. The lots were manufactured by BotanicLab (Brea, California). The study was halted and chemical analyses of the lots were performed. The analyses showed that all four lots of PC-SPES contained amounts of DES ranging from 0.1 μg/g to 32.7μg/g, and that one lot contained varying amounts of ethinyl estradiol. The authors concluded that the presence of these adulterants rendered their results inconclusive.[1]
Several nonrandomized clinical studies published between 1999 and 2003 described the results of clinical trials conducted before adulterants had been conclusively identified in PC-SPES lots and before it was known that there was significant variation in naturally occurring active agents, such as baicalein and licochalcone-A, in the lots. These studies, many of which enrolled small numbers of patients, did not identify the source of the lots that were used in the trials, nor did they identify where patients acquired PC-SPES.
In addition to the confounding effects of adulterants on the clinical trial results discussed below, the fact that an optimal dose of PC-SPES remains undetermined and that dose varies among these studies makes it difficult to compare their findings.
In a retrospective study of 23 consecutive patients with AI disease, charts were evaluated for patients' responses to PC-SPES and the occurrence of any toxicity. There is no report of where the patients acquired their PC-SPES or what lots were used. Patients were all seen between February and November in 1999. Patients ranged in age from 51 to 88 years, with a median age of 70 years. All had previous initial androgen ablation for a period of 6 months to 144 months. Ten patients had received chemotherapy, 13 had not. More than half of the patients with AI showed a post-therapy prostate-specific antigen (PSA) decline of 50% or greater. Median time to PSA progression was 6 months. The side effects were similar to those of estrogen therapy (gynecomastia and impotence). Other side effects were nausea/vomiting and diarrhea and to a lesser extent, allergic reactions, leg cramps, and leg swelling.[2]
In a prospective clinical trial of 16 men with stage D3 metastatic prostate cancer in which all patients had failed therapy and had disease progression, the effects of PC-SPES on pain, quality of life, and side effects were assessed. Previous therapy was either orchidectomy or a luteinizing hormone–releasing agonist with or without antiandrogen. Hormonal therapy was continued throughout the trial to avoid the known withdrawal effect of antiandrogen on PSA levels. There was a significant decrease in pain scores such that the 14 patients on analgesics required an average of 40% less analgesics while taking PC-SPES. PC-SPES treatment was associated with improved function and emotional and physical well-being. PSA levels declined significantly after PC-SPES therapy (>50%). Side effects were breast tenderness, deep venous thrombosis, and mild dyspepsia.[3,4]
In a study of 70 patients, 37 with androgen-dependent (AD) disease and 33 with AI disease, the AD cohort was treated with PC-SPES only after an initial treatment with prostatectomy, radiation, cryotherapy, and/or hormonal therapy. Median duration of PSA response was greater than 57 weeks. All patients in the AD cohort had PSA declines within a range of 80% to 100%, and two patients with bone metastases showed improvement on radiographic analysis. Within the AI cohort, 54% (19 of 35) had a PSA decrease of greater than 50%, with median time to nadir of 10 weeks and a median duration of 18 weeks. Eight of the 16 patients who had received ketoconazole therapy prior to PC-SPES also obtained a decrease of greater than 50% in their PSA values. Testosterone levels within the AD group decreased to castrate levels (<50 ng/mL) in 94% of patients (31 of 33), and libido (25 of 25) and potency (15 of 15) were lost in all patients who entered the study. Side effects were hot flashes, gynecomastia/gynecodynia, and thromboembolic effects in 3 of 70 patients. Although the results of this trial were promising for the treatment of both AI and AD prostate cancer, it is not possible to assess what was responsible for these effects. This trial used PC-SPES from one single lot, but the published study does not indicate the lot number. The research was completed before 2000. No attempt was made to assess the possible contamination of the product.[3,5]
A prospective clinical series assessed the ability of PC-SPES to lower serum PSA levels in 33 prostate cancer patients. The patients had either refused conventional therapy or had failed previous cryosurgery, radiation therapy, and/or hormonal therapy. No overt signs of disease progression were found in any of the patients. At 2 months, PSA levels had decreased by a mean of 52% in 27 of the 31 patients and had increased in two patients. Of the five patients who had hormone-refractory disease, all had decreased serum PSA levels.[3,6]
In a continuation of the previous study, a total of 69 patients with either AI or AD disease were separated into three study groups. Group one (n = 43) had undergone previous therapy, including hormonal; group two (n = 22) developed AI after treatment; and group three (n = 4) had not undergone previous therapy. The study assessed PC-SPES activity in suppressing PSA levels. Patients were given three capsules of PC-SPES 3 times per day. PSA levels and side effects were observed for 24 months.[7]
In group one, 82% of patients (32 of 39) had a decrease in PSA levels, with 20 patients having a decrease of greater than 50% at 2 months' follow-up; the decrease lasted for 24 months in two patients. In group two (AI patients), 90% (19 of 21) had a decrease in PSA at their 2-month follow-up, with 66% (14 of 21) having a decrease of greater than 50% in PSA levels. At 24 months, two patients had a decrease of 20% to 50% in pretreatment PSA levels. In group three, 50% (2 of 4) had a decrease of greater than 50% in PSA levels at 2 months, and the remaining two patients had an increase at 2 and 6 months. Eighty-two percent of study patients had a decreased PSA level after 2 months of therapy. Side effects included nipple tenderness (42%), gynecomastia (8%), hot flashes, and deep venous thrombosis.[7] In both Germany and the United Kingdom, PC-SPES–like formulations have been studied. A phase I trial of PC-Spes2 in the United Kingdom encountered tolerability problems due to diarrhea.[8]
- Oh WK, Kantoff PW, Weinberg V, et al.: Prospective, multicenter, randomized phase II trial of the herbal supplement, PC-SPES, and diethylstilbestrol in patients with androgen-independent prostate cancer. J Clin Oncol 22 (18): 3705-12, 2004. [PUBMED Abstract]
- Oh WK, George DJ, Hackmann K, et al.: Activity of the herbal combination, PC-SPES, in the treatment of patients with androgen-independent prostate cancer. Urology 57 (1): 122-6, 2001. [PUBMED Abstract]
- Pirani JF: The effects of phytotherapeutic agents on prostate cancer: an overview of recent clinical trials of PC SPES. Urology 58 (2 Suppl 1): 36-8, 2001. [PUBMED Abstract]
- Pfeifer BL, Pirani JF, Hamann SR, et al.: PC-SPES, a dietary supplement for the treatment of hormone-refractory prostate cancer. BJU Int 85 (4): 481-5, 2000. [PUBMED Abstract]
- Small EJ, Frohlich MW, Bok R, et al.: Prospective trial of the herbal supplement PC-SPES in patients with progressive prostate cancer. J Clin Oncol 18 (21): 3595-603, 2000. [PUBMED Abstract]
- de la Taille A, Hayek OR, Buttyan R, et al.: Effects of a phytotherapeutic agent, PC-SPES, on prostate cancer: a preliminary investigation on human cell lines and patients. BJU Int 84 (7): 845-50, 1999. [PUBMED Abstract]
- de la Taille A, Buttyan R, Hayek O, et al.: Herbal therapy PC-SPES: in vitro effects and evaluation of its efficacy in 69 patients with prostate cancer. J Urol 164 (4): 1229-34, 2000. [PUBMED Abstract]
- Shabbir M, Love J, Montgomery B: Phase I trial of PC-Spes2 in advanced hormone refractory prostate cancer. Oncol Rep 19 (3): 831-5, 2008. [PUBMED Abstract]
Adverse Effects
Adverse effects of PC-SPES treatment were similar to those of hormonal drugs. The percentages indicate the approximate low-to-high range of side effects reported in the studies. It is difficult to compile accurate numbers from all studies reporting side effects because they are not consistently reported. Some studies concatenated categories of side effects, some did not report specific numbers or percentages, and some reported a few side effects while not reporting others. The following references indicate the studies from which the percentages come:
- Gynecomastia (8%–8.7%).[1-6]
- Nipple tenderness (34.8%–100%).[1-7]
- Dyspepsia/nausea (15.7%–21.7%).[2-7]
- Fatigue (8%–17.1%).[1-5]
- Diarrhea (13%–38.6%).[1-5]
- Leg cramps/swelling (2%–68.5%).[1-5]
- Cardiovascular problems/angina (4.3%–7%).[1-5]
- Hot flashes (4.3%–34%).[1-5]
- Decreased libido (6.2%–100%).[5,7]
- Erectile dysfunction (single case report).[8]
- Thromboembolic effects (5%–6.2%).[5,6]
- Oh WK, George DJ, Hackmann K, et al.: Activity of the herbal combination, PC-SPES, in the treatment of patients with androgen-independent prostate cancer. Urology 57 (1): 122-6, 2001. [PUBMED Abstract]
- Oh WK, George DJ, Kantoff PW: Rapid rise of serum prostate specific antigen levels after discontinuation of the herbal therapy PC-SPES in patients with advanced prostate carcinoma: report of four cases. Cancer 94 (3): 686-9, 2002. [PUBMED Abstract]
- de la Taille A, Buttyan R, Hayek O, et al.: Herbal therapy PC-SPES: in vitro effects and evaluation of its efficacy in 69 patients with prostate cancer. J Urol 164 (4): 1229-34, 2000. [PUBMED Abstract]
- de la Taille A, Hayek OR, Buttyan R, et al.: Effects of a phytotherapeutic agent, PC-SPES, on prostate cancer: a preliminary investigation on human cell lines and patients. BJU Int 84 (7): 845-50, 1999. [PUBMED Abstract]
- Small EJ, Frohlich MW, Bok R, et al.: Prospective trial of the herbal supplement PC-SPES in patients with progressive prostate cancer. J Clin Oncol 18 (21): 3595-603, 2000. [PUBMED Abstract]
- Pfeifer BL, Pirani JF, Hamann SR, et al.: PC-SPES, a dietary supplement for the treatment of hormone-refractory prostate cancer. BJU Int 85 (4): 481-5, 2000. [PUBMED Abstract]
- DiPaola RS, Zhang H, Lambert GH, et al.: Clinical and biologic activity of an estrogenic herbal combination (PC-SPES) in prostate cancer. N Engl J Med 339 (12): 785-91, 1998. [PUBMED Abstract]
- Moyad MA, Pienta KJ, Montie JE: Use of PC-SPES, a commercially available supplement for prostate cancer, in a patient with hormone-naive disease. Urology 54 (2): 319-23; discussion 323-4, 1999. [PUBMED Abstract]
Summary of the Evidence for PC-SPES
To assist readers in evaluating the results of human studies of integrative, alternative, and complementary therapies for cancer, the strength of the evidence (i.e., the levels of evidence) associated with each type of treatment is provided whenever possible. To qualify for a level of evidence analysis, a study must:
- Be published in a peer-reviewed scientific journal.
- Report on therapeutic outcome or outcomes, such as tumor response, improvement in survival, or measured improvement in quality of life.
- Describe clinical findings in sufficient detail that a meaningful evaluation can be made.
The lack of consistent composition of PC-SPES due to varying concentrations of adulterants makes it difficult to determine the effects of PC-SPES in humans; therefore, no level of evidence analysis is possible for this treatment. At this time, the use of PC-SPES as a treatment for cancer cannot be recommended outside the context of well-designed clinical trials.
For additional information about levels of evidence analysis, refer to Levels of Evidence for Human Studies of Integrative, Alternative, and Complementary Therapies.
Latest Updates to This Summary (07/27/2017)
The PDQ cancer information summaries are reviewed regularly and updated as new information becomes available. This section describes the latest changes made to this summary as of the date above.
Editorial changes were made to this summary.
This summary is written and maintained by the PDQ Integrative, Alternative, and Complementary Therapies Editorial Board, which is editorially independent of NCI. The summary reflects an independent review of the literature and does not represent a policy statement of NCI or NIH. More information about summary policies and the role of the PDQ Editorial Boards in maintaining the PDQ summaries can be found on the About This PDQ Summary and PDQ® Cancer Information for Health Professionals pages.
About This PDQ Summary
Purpose of This Summary
This PDQ cancer information summary for health professionals provides comprehensive, peer-reviewed, evidence-based information about the use of PC-SPES in the treatment of people with cancer. It is intended as a resource to inform and assist clinicians in the care of their patients. It does not provide formal guidelines or recommendations for making health care decisions.
Reviewers and Updates
This summary is reviewed regularly and updated as necessary by the PDQ Integrative, Alternative, and Complementary Therapies Editorial Board, which is editorially independent of the National Cancer Institute (NCI). The summary reflects an independent review of the literature and does not represent a policy statement of NCI or the National Institutes of Health (NIH).
Board members review recently published articles each month to determine whether an article should:
- be discussed at a meeting,
- be cited with text, or
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Changes to the summaries are made through a consensus process in which Board members evaluate the strength of the evidence in the published articles and determine how the article should be included in the summary.
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Levels of Evidence
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PDQ® Integrative, Alternative, and Complementary Therapies Editorial Board. PDQ PC-SPES. Bethesda, MD: National Cancer Institute. Updated <MM/DD/YYYY>. Available at: https://www.cancer.gov/about-cancer/treatment/cam/hp/pc-spes-pdq. Accessed <MM/DD/YYYY>. [PMID: 26389352]
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