VR-3848, a novel peptide derived from Euphobiaceae, induces mitochondria-dependent apoptosis in human leukemia cells.
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.
Uthaisang
Wanlaya
W
Department of Chemistry, Faculty of Science, Mahidol University, Bangkok 10400, Thailand.
Reutrakul
Vichai
V
Krachangchaeng
Chongkon
C
Wilairat
Prapon
P
Fadeel
Bengt
B
D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D020169:Caspases / Q000378:metabolism; D045304:Cytochromes c / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D019665:Euphorbiaceae / Q000737:chemistry*; D006801:Humans; D019169:Jurkat Cells; D007938:Leukemia / Q000188:drug therapy* / Q000473:pathology; D008928:Mitochondria / Q000502:physiology*
D000972:Antineoplastic Agents, Phytogenic; D045304:Cytochromes c; D020169:Caspases