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Curcumin is a potent inhibitor of phenol sulfotransferase (SULT1A1) in human liver and extrahepatic tissues

1. Curcumin has anti-carcinogen effects and is under clinical evaluation as a potential colon cancer chemopreventive agent. The first aim was to see whether curcumin inhibited phenol sulfotransferase (SULT1A1) and, if so, to study the variability of the IC 50 of curcumin for SULT1A1 in 50 human liver samples. For comparative purposes, the inhibition of catechol sulfotransferase (SULT1A3) in five human liver specimens was studied. The second aim was to measure the IC 50 of curcumin against SULT1A1 in five samples of human duodenum, colon, kidney and lung. 2. Curcumin was a potent inhibitor of SULT1A1 in human liver; the mean ± SD and median of IC 50 were 14.1 ± 7.3 nM and 12.8 nM, respectively. The IC 50 ranged from 6.2 to 30.6 nM between the 5th and 95th percentiles and the fold of variation was 4.9. The distribution of IC 50 was positively skewed (skewness 1.2) and deviated from normality (p = 0.0004). 3. Curcumin inhibited human SULT1A3, and the inhibition was studied in five liver specimens with an IC 50 of 4324 ± 1026 nM. This inhibition was greater than the IC 50 of curcumin for SULT1A1 (p < 0.0001). 4. In the extrahepatic tissues, the IC 50 of curcumin for SULT1A1 was 25.9 ± 4.8 nM (duodenum), 25.4 ± 6.8 nM (colon), 23.4 ± 2.2 nM (kidney) and 25.6 ± 5.6 nM (lung). Inhibition in these tissues is greater than that of curcumin for SULT1A1 in human liver (p < 0.0001). 5. In conclusion, curcumin is a potent inhibitor of SULT1A1 in human liver, duodenum, colon, kidney and lung. The IC 50 of curcumin for SULT1A1 varied 4.9-fold in human liver. The comparison of the present data with those of the literature revealed that the IC 50 of curcumin in the liver and extrahepatic tissues is one order of magnitude lower that the peak serum concentration of curcumin after therapeutic doses of 4 g to humans.