MODULATION OF DRUG-INDUCED APOPTOSIS IN A HUMAN B-LYMPHOMA CELL-LINE (HT58)

The cytotoxic effect of etoposide (ETO), a topoisomerase II inhibitor, and staurosporine (STA), a non-selective protein kinase inhibitor, we re studied on a human lymphoma cell line of B-cell origin (HT58). Apop tosis, induced dose dependently by both drugs, was accompanied with nu cleosomal DNA fragmentation detected by flow cytometry. On the other h and, induction of cell death failed using phorbol ester (PMA), anti-Ig M antibody (a-IgM) or dexamethasone (DEX), although, all of these agen ts arrested the cells in Gl. Furthermore, PMA pretreatment retarded ET O-induced apoptosis, but enhanced STA cytotoxicity. DEX increased the sensitivity of cells to STA, but did not to ETO. Activity of STA or DE X was only slightly modified by a-IgM pretreatment. The results suppor t the possibility that different apoptotic pathways exist in HT58 cell s. The differences in pathways could be manifested either in the signa ling routes, or in the molecular effecters of apoptosis.