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Anticancer and Chemosensitizing Abilities of Cycloviolacin O2 from Viola odorata and Psyle Cyclotides from Psychotria leptothyrsa
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Division of Pharmacognosy.
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2010 (English)In: Biopolymers, ISSN 0006-3525, E-ISSN 1097-0282, Vol. 94, no 5, 617-625 p.Article in journal (Refereed) Published
Abstract [en]

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 mu M) were monitored in the presence and absence of doxorubicin (0.1-5 mu M) using cell proliferation assays to establish its chemosensitizing abilities. SYTOX Green assays were performed to verify membrane permeabilization and showed cellular disruption correlates with cyclo tide 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 cyclo tide 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 mu M), and coexposure to cyclotides significantly enhanced doxorubicin induced toxicity (IC50 = 0.39-0.76 mu M). This study documents several cyclotides with robust cytotoxicity that may be promising chemosensitizing agents against drug resistant breast cancer.

Place, publisher, year, edition, pages
2010. Vol. 94, no 5, 617-625 p.
Keyword [en]
anticancer, cyclotide, chemosensitizing, cycloviolacin O2, psyle
National Category
Pharmaceutical Sciences
Identifiers
URN: urn:nbn:se:uu:diva-136486DOI: 10.1002/bip.21435ISI: 000282930400008OAI: oai:DiVA.org:uu-136486DiVA: diva2:377546
Available from: 2010-12-14 Created: 2010-12-13 Last updated: 2017-12-11Bibliographically approved

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