Didemnin B induces apoptosis in proliferating but not resting peripheral blood mononuclear cells.
We have previously shown that didemnin B, a branched cyclic depsipeptide composed of seven amino acids and two hydroxy acids, can induce rapid and complete apoptosis in HL-60 cells (Grubb, D.R. et al. (1995) Biochem. Biophys. Res. Commun. 215, 1130-1136). We now report that didemnin B can induce apoptosis in a wide range of transformed cell lines. Resting normal lymphocytes, however, are apparently unaffected by exposure to the drug. To investigate whether cell transformation, and/or cell proliferation is necessary for didemnin B to induce apoptosis, we examined the effect of didemnin B on freshly harvested human lymphocytes before and after stimulation with concanavalin A. Didemnin B induced apoptosis in normal lymphocytes only after mitogenic stimulation and therefore warrants further examination for its potential as a chemotherapeutic agent, especially for treatment of leukemia.
Department of Biochemistry and Molecular Biology, School of Biomedical Sciences, Monash University, 100 Wellington Rd, Melbourne 3800, Australia.
M A
MA
Baker
D R
DR
Grubb
A
A
Lawen
D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D002455:Cell Division / Q000187:drug effects* / Q000502:physiology; D002461:Cell Line, Transformed / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D002478:Cells, Cultured; D053938:DNA Fragmentation / Q000187:drug effects / Q000502:physiology; D047630:Depsipeptides; D015536:Down-Regulation / Q000187:drug effects / Q000502:physiology; D006801:Humans; D007938:Leukemia / Q000188:drug therapy*; D007963:Leukocytes, Mononuclear / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D008854:Microscopy, Electron; D010456:Peptides, Cyclic / Q000494:pharmacology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000187:drug effects / Q000378:metabolism
D000970:Antineoplastic Agents; D047630:Depsipeptides; D010456:Peptides, Cyclic; D019253:Proto-Oncogene Proteins c-bcl-2; C030051:didemnins