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Antiproliferative effect of verapamil alone on brain tumor cells in vitro
W F Schmidt1, K R Huber, R S Ettinger
1Department of Pediatrics, School of Medicine, University of South Carolina, Columbia 20203.
Abstract:
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.
Insights
Verapamil, a calcium channel blocker, shows a reversible antiproliferative effect on pediatric brain tumor cell lines. This drug inhibits tumor cell growth and synthesis of DNA, RNA, and protein, offering potential for cancer therapy.
Area of Science:
- Oncology
- Pharmacology
- Cell Biology
Background:
- Calcium channel blockers (CCBs) are known to enhance standard chemotherapy efficacy by overcoming drug resistance.
- The direct impact of CCBs on tumor cell proliferation and cellular processes remains largely uncharacterized.
Purpose of the Study:
- To investigate the in vitro effects of the calcium channel blocker verapamil on human pediatric tumor cell lines.
- To determine verapamil's impact on tumor cell growth, synthesis, and cell cycle progression.
Main Methods:
- Human medulloblastoma, pinealoblastoma, glioma, and neuroblastoma cell lines were treated with varying concentrations of verapamil.
- Cell proliferation, DNA, RNA, and protein synthesis were measured.
- DNA flow cytometry was used to analyze cell cycle distribution.
Main Results:
- Verapamil exhibited a reversible antiproliferative effect on all tested tumor cell lines, with 50% growth inhibition at 25-50 microM.
- Complete growth inhibition occurred at 100 microM verapamil, with resumed proliferation upon drug removal.
- Dose-dependent decreases in DNA, RNA, and protein synthesis were observed within minutes of verapamil addition.
- Cell cycle analysis revealed a reversible block throughout the cell cycle, with a slight G1 increase, in tumor and normal cells.
Conclusions:
- Verapamil demonstrates significant reversible antiproliferative activity against human pediatric tumor cell lines in vitro.
- The drug impacts fundamental cellular processes like nucleic acid and protein synthesis.
- Verapamil's cell cycle effects and reversibility suggest potential therapeutic applications in pediatric oncology.