Abstract
Lonidamine is an antispermatogenic and anticancer drug that is believed to act by inhibition of energy metabolism. In this study, the effects of Lonidamine on the concentration of intracellular free Ca 2+ of several tumor cell lines were assessed because of the important role that cytosolic Ca 2+ plays in cell viability and proliferation. The presence of 300 μM Lonidamine resulted in large elevations of cytosolic Ca 2+ (> 100nM) in AS-30D rat ascites hepatoma cells and in cultured EMT6 murine mammary adenocarcinoma cells but had little effect on cultured NCI-H345 human small cell lung cancer cells. The apparent EC 50 for Lonidamine was approximately 175 μM. The source of elevated cytosolic Ca 2+ was primarily intracellular stores, and the effects of Lonidamine on Ca 2+ efflux from these stores did not appear to be due to an ionophoretic action of this compound or to a decline in the level of cellular ATP. These results indicate that the Ca 2+ homeostasis of certain lines of tumor cells is specifically altered by Lonidamine at concentrations known to affect cell proliferation.
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