IN-VITRO TESTING OF CALCIUM-CHANNEL BLOCKERS AND CYTOTOXIC CHEMOTHERAPY IN B-CELL LOW-GRADE NON-HODGKINS-LYMPHOMA

The flux of calcium forms an important intracellular messenger system. The bcl-2 oncoprotein is thought to make cells resistant to a variety of insults, including cytotoxic drugs, by the suppression of apoptosi s, which appears to involve the repartitioning of intracellular calciu m. Three drugs that affect calcium pathways and may influence this rep artitioning, i.e. dantrolene, azumolene (a water-soluble dantrolene an alogue) and nimodipine, were studied in cell culture, using both a tra nsformed follicle centre lymphoma cell line and primary culture of lym phoma cells in vitro in a manner that resulted in a growth pattern clo sely resembling that of the malignancy in vivo. Dantrolene and azumole ne were potent inducers of cell death in both systems reducing the via ble cell count by 70-90% in comparison with normal controls. Nimodipin e, in comparison. appeared to have no significant effect. These result s obtained in an in vitro setting suggest that further evaluation of d antrolene and azumolene for the treatment of low-grade non-Hodgkin's l ymphoma is warranted.