Most solid
tumor cells are less sensitive to apoptosis induced by anticancer drugs than hematopoietic
cancer cells. However, the mechanisms of the different responses to apoptosis in these cell types remain unknown. To explore this question, we used
B16 melanoma and EL-4
lymphoma cells as solid
tumor- and hematopoietic
cancer-derived cell lines, and examined the effects of two apoptosis inducers,
cytostatin and
bactobolin, on both cell lines. Apoptosis in B16 cells was induced strongly by
bactobolin, but weakly by
cytostatin. In contrast, apoptosis in EL-4 cells was induced strongly by
cytostatin, but weakly by
bactobolin. While
caspase-3 was activated upon induction of apoptosis in both cell lines,
Ac-DEVD-CHO, a specific inhibitor of
caspase-3, suppressed only the apoptosis in B16 cells. In B16 cells,
cyclins E, A, and B1 were decreased by strongly apoptosis-inducing
bactobolin prior to 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 apoptosis commitment, but neither
cyclin A nor B1 was decreased by weakly apoptosis-inducing
bactobolin. These results indicate that the dependency of apoptosis 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.