Antiproliferative Effect of Verapamil Alone on Brain Tumor Cells in Vitro1

Recent studies have shown that the calcium channel blockers, when combined with standard anticancer drugs, help overcome resistance that often develops to those drugs. Little is known about the effects of the calcium channel blockers themselves on tumor cells. We have studied the effects of one calcium channel blocker, vcrapamil, on human tumor cell lines in vitro. Our results show a reversible, antiproliferative action of vcrapamil on human medulloblastoma, pinealoblastoma, glioma, and neuroblastoma tumor lines established from pediatrie patients. Growth rates are inhibited 10 to 100% by 10 to 100 MMverapamil with 50% inhibition occurring between 25 and 50 UM verapamil. No cell line proliferates in 100 MMverapamil, yet washing the cells after 72 h of incubation with 100 MMverapamil results in resumed cell growth. Growth inhibition is accompanied by dose-dependent decreases in DNA, RNA, and protein synthesis which occur within minutes after addition of vera pamil. DNA flow cytometry on propidium iodide-stained nuclei shows that, after incubation for 48 h with 100 MMverapamil, the medulloblas toma and neuroblastoma tumor lines as well as normal, human foreskin and lung fibroblast cell lines are reversibly blocked throughout the cell cycle with slight increases in Gì. Verapamil appears to have no effect on nucleic acid precursors or on calcium influx or efflux in human medullo blastoma cells.