{'fraction_non_alphanumeric': 0.033203125, 'fraction_numerical': 0.009765625, 'mean_word_length': 5.485232067510548, 'pattern_counts': {'":': 0, '<': 1, '<?xml version=': 0, '>': 0, 'https://': 0, 'lorem ipsum': 0, 'www.': 0, 'xml': 0}, 'pii_count': 0, 'substrings_counts': 0, 'word_list_counts': {'cursed_substrings.json': 0, 'profanity_word_list.json': 0, 'sexual_word_list.json': 0, 'zh_pornsignals.json': 0}}
Monitoring the anti‐cancer effects and chemosensitizing abilities of novel cyclotides from Psychotria leptothyrsa

Cyclotides are plant proteins with exceptional structural stability, due to their cysteine knot motif and cyclic peptide backbone. Cycloviolacin O2 (CyO2), a cyclotide from Viola odorata (Violaceae family) has anti‐tumor effects and causes cell death by membrane permeabilization. Despite their history of use, little is known about cyclotide distribution in the Rubiaceae family. We observed that Psychotria leptothyrsa, a member of the Rubiaceae family, expresses six novel cyclotides, psyle A ‐ psyle F. Their structures were elucidated by RP‐HPLC, LC‐MS and MS/MS sequencing. In the breast cancer line, MCF‐7 and its drug resistant sub‐line MCF‐7/ADR, we monitored the cytotoxic effects of psyle cyclotides, by using MTT assays. Cytotoxicities were also measured in presence or absence of Doxorubicin (5 ‐ 0.1 µM). Psyle E showed a potent cytotoxic effect (IC50 < 1µM) comparable to CyO2. Furthermore, co‐exposure to CyO2 or psyle E significantly enhanced doxorubicin induced toxicity in MCF‐7/ADR cells. We used a Sytox Green pore formation assay to determine membrane permeabilization. Cy02 showed the highest pore formation ability, followed by psyle C and psyle A, which correlates with their chemosensitizing abilities. We document several novel cyclotides with potent anti‐cancer effects and demonstrate that cyclotides may be promising chemosensitizing agents against drug resistant cancers. Supported by LCRC.