Protein tyrosine kinase inhibitors prevent didemnin B-induced apoptosis in HL-60 cells.
Didemnin B induces rapid apoptosis in human promyeloid HL-60 cells with an optimal concentration of 1 microM (Grubb et al. (1995) Biochem. Biophys. Res. Commum. 215, 1130-1136), but little is known about how it does so. In order to determine whether protein tyrosine phosphorylation is involved in this rapid induction of apoptosis, HL-60 cells were pre-treated with tyrosine kinase inhibitors for 1 h before didemnin B treatment. Genistein, 2,5-dihydroxycinnamic acid methyl ester, and a range of tyrphostins inhibit didemnin B-induced apoptotic morphology in a concentration-dependent manner. DNA fragmentation induced by didemnin B is also inhibited by genistein, 2,5-dihydroxycinnamic acid methyl ester, and tyrphostins.
Johnson
K L
KL
Department of Biochemistry and Molecular Biology, Monash University, Clayton, Australia.
Vaillant
F
F
Lawen
A
A
D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D048429:Cell Size; D002934:Cinnamates / Q000494:pharmacology; D004247:DNA / Q000378:metabolism; D047630:Depsipeptides; D004591:Electrophoresis, Polyacrylamide Gel; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D019833:Genistein; D018922:HL-60 Cells; D006801:Humans; D007529:Isoflavones / Q000494:pharmacology; D008856:Microscopy, Fluorescence; D009570:Nitriles / Q000494:pharmacology; D010456:Peptides, Cyclic / Q000494:pharmacology*; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*
D000970:Antineoplastic Agents; D002934:Cinnamates; D047630:Depsipeptides; D004791:Enzyme Inhibitors; D007529:Isoflavones; D009570:Nitriles; D010456:Peptides, Cyclic; C030051:didemnins; C067472:methyl 2,5-dihydroxycinnamate; D004247:DNA; D019833:Genistein; D011505:Protein-Tyrosine Kinases