Department of Biochemistry and Molecular Biology, Monash University, Clayton, Australia.
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.