In vitro potentiation by lonidamine of the cytotoxic effect of adriamycin on primary and established breast cancer cell lines

Lonidamine is a new potential chemotherapeutic agent, relatively non-toxic, that can positively modulate the efficacy of several antineoplastic drugs. We evaluated the response of two established human breast cancer cell lines (MCF-7 and BRC-230) and of 20 primary breast cancer cell lines to lonidamine, either alone or in combination with adriamycin, the drug most widely used in the management of breast cancer. Different schedules were tested by varying either concentration of the drugs (LND: 10-150μg/ml; ADM: 0.10-0.15μg/ml), or time of exposure (1-96 hours), or sequence of administration (ADM → LND; LND → ADM; ADM + LND). Our results indicate slight sensitivity of the cell lines to lonidamine when used alone, whereas an increase of efficacy was noted when lonidamine was added for at least 24 hours after a 4 hour exposure to adriamycin. Such efficacy was significantly greater than that expected from an additive effect between the two drugs. We conclude that lonidamine, when given according to an appropriate schedule, enhances, in vitro, the efficacy of adriamycin. A correct employment of lonidamine in the management of breast cancer might therefore potentiate the therapeutic effect of adriamycin.