In vitro effect of lonidamine on the cytotoxicity of mitomycin C and BCNU in human colon adenocarcinoma cells.
The ability of lonidamine (LND), an energolytic derivative of indazole carboxylic acid, to modulate the cytotoxic activity of mitomycin C (MMC) and 1,3,bis(2-chloroethyl)-1-nitrosourea (BCNU) was investigated in two human adenocarcinoma cell lines (LoVo and HT29) expressing different sensitivity profiles to the drugs. After a 1-h treatment with MMC or BCNU, cells were postincubated for 24 h with 150-225 microM LND. In the LoVo cells, a synergistic interaction between LND and MMC or BCNU was observed at both LND concentrations. In HT29 cells, only additive effects of the drugs given in sequence were seen. Flow cytometric analysis indicated that LND was generally able to stabilise the cell cycle perturbations induced by MMC and BCNU in the two cell lines. The ability of LND to potentiate anticancer drug activity, and the consideration that LND causes side-effects different from those of conventional antitumour drugs, make this compound an attractive candidate for multidrug combination therapy in colon cancer.
Istituto Nazionale Tumori, Milan, Italy.
R
R
Villa
N
N
Zaffaroni
L
L
Orlandi
A
A
Bearzatto
A
A
Costa
R
R
Silvestrini
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000473:pathology; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002330:Carmustine / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D004357:Drug Synergism; D006801:Humans; D007191:Indazoles / Q000494:pharmacology*; D016685:Mitomycin / Q000494:pharmacology*; D014407:Tumor Cells, Cultured / Q000187:drug effects
D000970:Antineoplastic Agents; D007191:Indazoles; D016685:Mitomycin; D002330:Carmustine; C016371:lonidamine