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Mechanism of action of cytotoxic cyclotides: cycloviolacin O2 disrupts lipid membranes
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Division of Pharmacognosy.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Division of Pharmacognosy.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Division of Pharmacognosy.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Pharmacology.
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2007 (English)In: Journal of natural products (Print), ISSN 0163-3864, E-ISSN 1520-6025, Vol. 70, no 4, 643-647 p.Article in journal (Refereed) Published
Abstract [en]

In recent years, the cyclotides have emerged as the largest family of naturally cyclized proteins. Cyclotides display potent cytotoxic activity that varies with the structure of the proteins, and combined with their unique structure, they represent novel cytotoxic agents. However, their mechanism of action is yet unknown. In this work we show that disruption of cell membranes plays a crucial role in the cytotoxic effect of the cyclotide cycloviolacin O2 (1), which has been isolated from Viola odorata. Cell viability and morphology studies on the human lymphoma cell line U-937 GTB showed that cells exposed to 1 displayed disintegrated cell membranes within 5 min. Functional studies on calcein-loaded HeLa cells and on liposomes showed rapid concentration-dependent release of their respective internal contents. The present results show that cyclotides have specific membrane-disrupting activity.

Place, publisher, year, edition, pages
2007. Vol. 70, no 4, 643-647 p.
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Pharmaceutical Sciences
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URN: urn:nbn:se:uu:diva-103776DOI: 10.1021/np070007vISI: 000246007200028PubMedID: 17378610OAI: oai:DiVA.org:uu-103776DiVA: diva2:218693
Available from: 2009-05-20 Created: 2009-05-20 Last updated: 2017-12-13Bibliographically approved

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Göransson, Ulf

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