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

Uthaisang, Wanlaya; Reutrakul, Vichai; Krachangchaeng, Chongkon; Wilairat, Prapon; Fadeel, Bengt

doi:10.1016/j.canlet.2004.01.024

« Previous Next »Cancer Letters
Volume 208, Issue 2 , Pages 171-178, 28 May 2004

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

Wanlaya Uthaisang
- Department of Biochemistry, Faculty of Science, Mahidol University, Bangkok 10400, Thailand
- Institute of Environmental Medicine, Division of Toxicology, Nobels väg 13, Karolinska Institutet, 171 77 Stockholm, Sweden
Vichai Reutrakul
- Department of Chemistry, Faculty of Science, Mahidol University, Bangkok 10400, Thailand
Chongkon Krachangchaeng
- Department of Chemistry, Faculty of Science, Mahidol University, Bangkok 10400, Thailand
Prapon Wilairat
- Department of Biochemistry, Faculty of Science, Mahidol University, Bangkok 10400, Thailand
Bengt Fadeel
- Institute of Environmental Medicine, Division of Toxicology, Nobels väg 13, Karolinska Institutet, 171 77 Stockholm, Sweden
- Corresponding author. Tel.: +46-8-728-7556; fax: +46-8-32-90-41

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.

Keywords: Apoptosis, Caspase, Euphobiaceae, Mitochondria, Peptide