NON-IONOPHORETIC ELEVATION OF INTRACELLULAR CA2+ BY LONIDAMINE

Lonidamine is an antispermatogenic and anticancer drug that is believe d to act by inhibition of energy metabolism. In this study, the effect s of Lonidamine on the concentration of intracellular. free Ca2+ of se veral tumor cell lines were assessed because of the important role tha t cytosolic Ca2+ plays in cell viability and proliferation. The presen ce of 300 muM Lonidamine resulted in large elevations of cytosolic Ca2 + (> 100 nM) 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 EC50 for Lo nidamine was approximately 175 muM. The source of elevated cytosolic C a2+ was primarily intracellular stores, and the effects of Lonidamine on Ca2+ efflux from these stores did not appear to be due to an ionoph oretic action of this compound or to a decline in the level of cellula r ATP. These results indicate that the Ca2+ homeostasis of certain lin es of tumor cells is specifically altered by Lonidamine at concentrati ons known to affect cell proliferation.