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Volume 208, Issue 2, Pages 171-178 (28 May 2004)


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VR-3848, a novel peptide derived from Euphobiaceae, induces mitochondria-dependent apoptosis in human leukemia cells

Wanlaya Uthaisangac, Vichai Reutrakulb, Chongkon Krachangchaengb, Prapon Wilairata, Bengt FadeelcCorresponding Author Informationemail address

Received 14 November 2003; received in revised form 19 December 2003; accepted 21 January 2004.

Abstract 

VR-3848, a novel peptide derived from Euphobiaceae, is shown herein to induce apoptosis at nanomolar concentrations in the leukemic Jurkat cell line. Apoptosis was associated with activation of caspases, release of cytochrome c from mitochondria, fragmentation of nuclear DNA, and externalization of phosphatidylserine on the cell surface. Overexpression of mitochondria-targeted Bcl-2 abrogated VR-3848-induced killing in this model. Primary human interleukin (IL)-2-activated T lymphocytes were considerably less sensitive to VR-3848-induced apoptosis as compared to Jurkat cells. VR-3848 thus holds the promise of being a potent and selective anti-cancer agent that deserves further exploration.

a Department of Biochemistry, Faculty of Science, Mahidol University, Bangkok 10400, Thailand

b Department of Chemistry, Faculty of Science, Mahidol University, Bangkok 10400, Thailand

c Institute of Environmental Medicine, Division of Toxicology, Nobels väg 13, Karolinska Institutet, 171 77 Stockholm, Sweden

Corresponding Author InformationCorresponding author. Tel.: +46-8-728-7556; fax: +46-8-32-90-41

PII: S0304-3835(04)00103-X

doi:10.1016/j.canlet.2004.01.024


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