INTRACELLULAR CA2-TUMOR CELLS( MEDIATES THE CYTOTOXICITY INDUCED BY BEPRIDIL AND BENZAMIL IN HUMAN BRAIN)

The effects of bepridil and benzamil, known Na+-Ca2+ exchange blockers , on the growth of human brain tumor cells were evaluated using SK-N-M C human neuroblastoma and U-373 MG human astrocytoma cells as model ce llular systems. These drugs induced cytotoxicity in both cells in a do se-dependent manner. Agonist (2% fetal bovine serum) alone induced a r apid increased intracellular Ca2+ concentration and then it returned t o the basal level. However, the pretreatments of these drugs resulted in a more sustained high intracellular Ca2+ concentration mobilized by an agonist. Moreover, BAPTA/AM, an intracellular Ca2+ chelator, signi ficantly blocked the cytotoxicity induced by these drugs. These result s suggest that bepridil and benzamil act as effective inhibitors of in vitro growth of human brain tumor cells and that intracellular Ca2+ m ay be involved in the mechanism of actions of these agents.