CLOTRIMAZOLE INHIBITS CELL-PROLIFERATION IN-VITRO AND IN-VIVO

Cell proliferation is critically dependent on the regulated movement o f ions across various cellular compartments. The antimycotic drug clot rimazole (CLT) has been shown to inhibit movement of Ca2+ and K+ acros s the plasma membrane. Our results show that CLT inhibits the rate of cell proliferation of normal and cancer cell fines in a reversible and dose-dependent manner in vitro. Moreover, CLT depletes the intracellu lar Ca2+ stores and prevents the rise in cytosolic Ca2+ that normally follows mitogenic stimulation. In mice with severe combined immunodefi ciency disease (SCID) and inoculated intravenously with MM-RU human me lanoma cells, daily subcutaneous injections of CLT induced a significa nt reduction in the number of lung metastases. Modulation of early ion ic mitogenic: signals and potent inhibition of cell proliferation both in vitro and in vivo are new and potentially useful clinical effects of CLT.