title: Non-ionophoretic elevation of intracellular Ca2+ by Lonidamine.
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 Ca2+ of several tumor cell lines were assessed because of the important role that cytosolic Ca2+ plays in cell viability and proliferation. The presence of 300 microM 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 Lonidamine was approximately 175 microM. The source of elevated cytosolic Ca2+ was primarily intracellular stores, and the effects of Lonidamine on Ca2+ 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 Ca2+ homeostasis of certain lines of tumor cells is specifically altered by Lonidamine at concentrations known to affect cell proliferation.
authors.affiliation: Laboratory for Cell Metabolism and Pharmacokinetics, Regina Elena Institute for Cancer Research, Rome, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Castiglione
authors.forename: K A
authors.initials: KA
authors.lastname: Kennedy
authors.forename: A
authors.initials: A
authors.lastname: Floridi
authors.forename: G
authors.initials: G
authors.lastname: Fiskum
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D000988:Antispermatogenic Agents / Q000494:pharmacology*; D001665:Binding Sites; D002118:Calcium / Q000378:metabolism*; D002460:Cell Line / Q000187:drug effects; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004533:Egtazic Acid; D016257:Fura-2; D006801:Humans; D007191:Indazoles / Q000494:pharmacology*; D007425:Intracellular Membranes / Q000187:drug effects / Q000378:metabolism; D008081:Liposomes; D051381:Rats; D014407:Tumor Cells, Cultured / Q000187:drug effects; D015854:Up-Regulation
chemical_list: D000970:Antineoplastic Agents; D000988:Antispermatogenic Agents; D007191:Indazoles; D008081:Liposomes; D004533:Egtazic Acid; D002118:Calcium; D016257:Fura-2; C016371:lonidamine