PROTEIN-TYROSINE KINASE INHIBITORS PREVENT DIDEMNIN B-INDUCED APOPTOSIS IN HL-60 CELLS

Didemnin B induces rapid apoptosis in human promyeloid HL-60 cells wit h an optimal concentration of 1 mu M (Grubb et al, (1995) Biochem. Bio phys. Res. Commun. 215, 1130-1136), but little is known about how it d oes so. In order to determine whether protein tyrosine phosphorylation is involved in this rapid induction of apoptosis, HL-60 cells were pr e-treated with tyrosine kinase inhibitors for 1 h before didemnin B tr eatment, Genistein, 2,5-dihydroxycinnamic acid methyl ester, and a ran ge 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 e ster, and tyrphostins.