In vitro potentiation by lonidamine of the sc-RIP saporin 6 effect in a human metastatic breast cancer cell line.

The ability of Lonidamine (LND), an energolytic derivative of indazole-carboxylic acid, to modulate the antiproliferative effect of the single-chain ribosome-inactivating protein Saporin 6 (SO 6) was investigated in the human MAST breast cancer cell line, recently established from an ascitic effusion of a ductal carcinoma, by analysis of protein synthesis inhibition and of colony formation in vitro. Different schedules were tested varying with regard to time of exposure (0-24 h), concentration of the drugs (0.01- > 10 micrograms/ml SO 6; 25-100 micrograms/ml LND) and sequence of administration (LND- > SO 6; SO 6- > LND; SO 6+LND). Results indicate that the marginal activity exerted here by each drug when tested independently is highly potentiated by the combination treatments, the cytotoxicity becoming significantly greater than that expected from an additive effect between the two drugs. In particular, a strong synergistic effect is obtained when SO 6 preceedes LND, with a reduction of the SO 6 IC 50 from 1.3 x 10(-7) M to 2.6 x 10(-9) M.