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

Jpn J Cancer Res. 1999 Feb;90(2):219-25. doi: 10.1111/j.1349-7006.1999.tb00736.x.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibiotics, Antineoplastic / pharmacology*
  • Apoptosis / drug effects*
  • Benzopyrans / pharmacology
  • Caspases / metabolism
  • DNA Fragmentation
  • Lymphoma / pathology*
  • Melanoma, Experimental / pathology*
  • Mice
  • Organophosphates / pharmacology*
  • Proto-Oncogene Proteins c-bcl-2 / physiology
  • Pyrones / pharmacology*
  • Tumor Cells, Cultured


  • Antibiotics, Antineoplastic
  • Benzopyrans
  • Organophosphates
  • Proto-Oncogene Proteins c-bcl-2
  • Pyrones
  • cytostatin
  • bactobolin
  • Caspases