VINORELBINE INDUCES APOPTOSIS AND CASPASE-3 (CPP32) EXPRESSION IN LEUKEMIA AND LYMPHOMA-CELLS - A COMPARISON WITH VINCRISTINE

Vinorelbine (NVB) is a novel vinca alkaloid FDA approved for use in so me advanced carcinomas. However, its role in non-Hodgkin's lymphoma (N HL) is still not well defined. NVB is an antimicrotubule agent, but as yet, it is not known whether it induces apoptosis. By flow cytometry using nuclear staining (propidium iodide) and annexin V, we demonstrat ed that NVB and vincristine (VCR) induced both mitotic arrest and apop tosis in leukemia and lymphoma cells, in a drug exposure time dependen t manner. Cell cycle kinetics in 3 different cell lines varied during vinca alkaloid treatment. The annexin V method showed that apoptosis, as opposed to necrosis, was the dominant mode of cell kill of chemosen sitive leukemia and lymphoma cells. Phosphatidylserine expression on t he cell surface was detectable as a hallmark of apoptosis at earlier d rug exposure when compared to conventional flow cytometry with PI stai ning. By Western blot analysis, we demonstrated that CPP32 or caspase- 3, a critical apoptosis inducer, and its active subunits p20 and p11 w ere upregulated in chemo- and apoptosis-sensitive lymphoma and leukemi a cells treated with NVB. Our data contributes to the emerging hypothe sis suggesting that widely divergent exogenous stimuli and chemotherap eutic agents carl effect apoptosis in cancer cells via different pathw ays involving the caspases. We believe that vinorelbine may be a poten tially important drug in the treatment of NHL in the future.