Antiproliferative effect of verapamil alone on brain tumor cells in vitro

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 calc...

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Bibliographic Details
Published in:Cancer research (Chicago, Ill.) Ill.), 1988-07, Vol.48 (13), p.3617-3621
Main Authors: SCHMIDT, W. F, HUBER, K. R, ETTINGER, R. S, NEUBERG, R. W
Format: Article
Language:English
Subjects:
Antineoplastic agents
Biological and medical sciences
Calcium - physiology
Cell Cycle - drug effects
Cell Division - drug effects
Dose-Response Relationship, Drug
General aspects
Glioma - pathology
Humans
In Vitro Techniques
Medical sciences
Medulloblastoma - pathology
Nucleic Acids - biosynthesis
Pharmacology. Drug treatments
Protein Biosynthesis
Tumor Cells, Cultured
Verapamil - pharmacology
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Summary: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, verapamil, on human tumor cell lines in vitro. Our results show a reversible, antiproliferative action of verapamil on human medulloblastoma, pinealoblastoma, glioma, and neuroblastoma tumor lines established from pediatric patients. Growth rates are inhibited 10 to 100% by 10 to 100 microM verapamil with 50% inhibition occurring between 25 and 50 microM verapamil. No cell line proliferates in 100 microM verapamil, yet washing the cells after 72 h of incubation with 100 microM verapamil 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 verapamil. DNA flow cytometry on propidium iodide-stained nuclei shows that, after incubation for 48 h with 100 microM verapamil, the medulloblastoma 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 G1. Verapamil appears to have no effect on nucleic acid precursors or on calcium influx or efflux in human medulloblastoma cells.
ISSN:0008-5472
1538-7445