Differential induction of apoptosis in B16 melanoma and EL-4 lymphoma cells by cytostatin and bactobolin

Most solid tumor cells are less sensitive to apoptosis induced by anticance r drugs than hematopoietic cancer cells. However, the mechanisms of the dif ferent responses to apoptosis in these cell types remain unknown. To explor e this question, we used B16 melanoma and EL-4 lymphoma cells as solid tumo r- and hematopoietic cancer-derived cell lines, and examined the effects of two apoptosis inducers, cytostatin and bactobolin, on both cell lines. Apo ptosis in B16 cells was induced strongly by bactobolin, but weakly by cytos tatin. In contrast, apoptosis in EL-4 cells was induced strongly by cytosta tin, but weakly by bactobolin. While caspase-3 was activated upon induction of apoptosis in both cell lines, Ac-DEVD-CHO, a specific inhibitor of casp ase-3, suppressed only the apoptosis in B16 cells. In B16 cells, cyclins E, A, and B1 were decreased by strongly apoptosis-inducing bactobolin prior t o apoptosis commitment, but cyclin E was not decreased by weakly apoptosis- inducing cytostatin. On the other hand, in EL-4 cells cyclins D1, E, A, and B1 were decreased by strongly apoptosis-inducing cytostatin prior to apopt osis commitment, but neither cyclin A nor B1 was decreased by weakly apopto sis-inducing bactobolin. These results indicate that the dependency of apop tosis induction on caspase activity is different between the two cell lines . Furthermore, there may be an inverse correlation between specific cyclins and apoptosis induction in the two cell lines.