Abstract
Cell proliferation is critically dependent on the regulated movement of ions across various cellular compartments. The antimycotic drug clotrimazole (CLT) has been shown to inhibit movement of Ca2+ and K+ across the plasma membrane. Our results show that CLT inhibits the rate of cell proliferation of normal and cancer cell lines in a reversible and dose-dependent manner in vitro. Moreover, CLT depletes the intracellular Ca2+ stores and prevents the rise in cytosolic Ca2+ that normally follows mitogenic stimulation. In mice with severe combined immunodeficiency disease (SCID) and inoculated intravenously with MM-RU human melanoma cells, daily subcutaneous injections of CLT induced a significant reduction in the number of lung metastases. Modulation of early ionic mitogenic signals and potent inhibition of cell proliferation both in vitro and in vivo are new and potentially useful clinical effects of CLT.
MeSH terms
-
3T3 Cells / drug effects
-
3T3 Cells / metabolism
-
Animals
-
Antineoplastic Agents / pharmacology
-
Antineoplastic Agents / therapeutic use
-
Calcium / metabolism
-
Calcium Channel Blockers / pharmacology*
-
Calcium Channel Blockers / therapeutic use
-
Cattle
-
Cell Compartmentation
-
Cell Division / drug effects*
-
Cell Line
-
Clotrimazole / pharmacology*
-
Clotrimazole / therapeutic use
-
Endothelium, Vascular / cytology
-
Endothelium, Vascular / drug effects
-
Female
-
Growth Inhibitors / pharmacology*
-
Growth Inhibitors / therapeutic use
-
Humans
-
Intracellular Fluid / drug effects
-
Lung Neoplasms / drug therapy
-
Lung Neoplasms / secondary
-
Male
-
Melanoma / drug therapy
-
Melanoma / secondary
-
Mice
-
Mice, SCID
-
Neoplasm Transplantation
-
Neoplastic Stem Cells / drug effects
-
Neoplastic Stem Cells / pathology
-
Rats
-
Tumor Cells, Cultured
Substances
-
Antineoplastic Agents
-
Calcium Channel Blockers
-
Growth Inhibitors
-
Clotrimazole
-
Calcium