Anticancer and chemosensitizing abilities of cycloviolacin O2 from Viola odorata and psyle cyclotides from Psychotria leptothyrsa

• Published in: Biopolymers 2010, Vol.94 (5), p.617-625
• Main Authors: Gerlach, Samantha L., Rathinakumar, Ramesh, Chakravarty, Geetika, Göransson, Ulf, Wimley, William C., Darwin, Steven P., Mondal, Debasis
• Format: Article
• Language: English
• Subjects: anticancer; chemosensitizing; cyclotide; cycloviolacin O2; FARMACI; PHARMACY; psyle
• ISSN: 0006-3525; 1097-0282; 1097-0282
• DOI: 10.1002/bip.21435

Cycloviolacin O2 (CyO2), a cyclotide from Viola odorata (Violaceae) has antitumor effects and causes cell death by membrane permeabilization. In the breast cancer line, MCF‐7 and its drug resistant subline MCF‐7/ADR, the cytotoxic effects of CyO2 (0.2–10 μM) were monitored in the presence and absence of doxorubicin (0.1–5 μM) using cell proliferation assays to establish its chemosensitizing abilities. SYTOX Green assays were performed to verify membrane permeabilization and showed cellular disruption correlates with cyclotide chemosensitization. Fluorescence microscopy studies demonstrated increased cellular internalization of doxorubicin in drug resistant cells when coexposed to CyO2. Interestingly, CyO2 did not produce significant membrane disruption in primary human brain endothelial cells, which suggested cyclotide specificity toward induced pore formation in highly proliferating tumor cells. Furthermore, three novel cyclotides (psyle A, C and E) from Psychotria leptothyrsa (Rubiaceae) were also monitored for cytotoxic activity. The cyclotides displayed potent cytotoxicity (IC50 = 0.64–>10 μM), and coexposure to cyclotides significantly enhanced doxorubicin induced toxicity (IC50 = 0.39–0.76 μM). This study documents several cyclotides with robust cytotoxicity that may be promising chemosensitizing agents against drug resistant breast cancer. © 2010 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 94: 617–625, 2010. This article was originally published online as an accepted preprint. The “Published Online” date corresponds to the preprint version. You can request a copy of the preprint by emailing the Biopolymers editorial office at [e-mail]