Intracellular Ca2+ mediates the cytotoxicity induced by bepridil and benzamil in human brain tumor cells.
The effects of bepridil and benzamil, known Na(+)-Ca2+ exchange blockers, on the growth of human brain tumor cells were evaluated using SK-N-MC human neuroblastoma and U-373 MG human astrocytoma cells as model cellular systems. These drugs induced cytotoxicity in both cells in a dose-dependent manner. Agonist (2% fetal bovine serum) alone induced a rapid increased intracellular Ca2+ concentration and then it returned to 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, significantly blocked the cytotoxicity induced by these drugs. These results suggest that bepridil and benzamil act as effective inhibitors of in vitro growth of human brain tumor cells and that intracellular Ca2+ may be involved in the mechanism of actions of these agents.
Lee
Y S
YS
Department of Neurological Surgery, Loyola University Medical Center, Maywood, IL 60153.
Sayeed
M M
MM
Wurster
R D
RD
D000584:Amiloride / Q000031:analogs & derivatives* / Q000633:toxicity; D001254:Astrocytoma / Q000188:drug therapy; D015764:Bepridil / Q000633:toxicity*; D001932:Brain Neoplasms / Q000188:drug therapy*; D002118:Calcium / Q000502:physiology*; D002455:Cell Division / Q000187:drug effects; D003593:Cytoplasm / Q000378:metabolism; D006801:Humans; D009447:Neuroblastoma / Q000188:drug therapy; D009532:Nickel / Q000633:toxicity; D014407:Tumor Cells, Cultured
C013407:benzamil; D015764:Bepridil; D000584:Amiloride; D009532:Nickel; D002118:Calcium