EFFECT OF LONIDAMINE ON THE CYTOTOXIC ACTIVITY OF CISPLATIN, MITOMYCIN-C AND BCNU IN HUMAN OVARIAN AND COLON-CARCINOMA CELLS

The ability of lonidamine (LND), an energolytic derivative of indazole carboxylic acid, to modulate the cytotoxic activity of cisplatin (CDD P), mitomycin C (MMC) and BCNU was investigated in established cell li nes of human ovarian and colon cancers. A 24 hour post-incubation with LND significantly potentiated the activity of a 1 hour CDDP treatment in both the sensitive (A2780) and resistant (A2780/Cp8) ovarian cell lines. Flow cytometric analysis showed that, in the resistant cell lin e, LND transformed the temporary G(2)+M cell accumulation induced by C DDP into a persistent block in S/G(2)+M phases. Again, in the A2780/Cp 8 cells, LND markedly enhanced the accumulation of DNA interstrand cro sslinks (DNA ISC) induced by the alkylating agent. As regards the colo n cancer cell lines, a 24 hour postincubation with LND enhanced the cy totoxicity of a 1 hour exposure to MMC or BCNU in both LoVo and HT29 c ells. Moreover, flow cytometric data indicated that LND generally stab ilized the cell cycle perturbations induced by MMC and BCNU in the two cell lines. On the whole, our results show that LND can positively mo dulate the activity of conventional anticancer agents and indicate thi s compound to be an attractive candidate for multidrug combination the rapies in ovarian and colon cancer.