Synergistic effect of probimane on anticancer cytotoxicity of doxorubicin in vitro.

Using 3-(4,5-dimethythiazole)-2,5-diphenyltetrazolium bromide (MTT) method, the effect of probimane (Pro) on doxorubicin (Dox) cytotoxicity was studied. Pro 0.313, 0.625, and 1.25 micrograms.ml-1 potentiated cytotoxicity of Dox in Ehrlich ascites carcinoma (EAC) cells. Incubation of EAC cells with Dox 10 micrograms.ml-1 and Pro 116.5, 233, and 466 micrograms.ml-1 resulted in an increase in intracellular drug accumulation from 0.69 +/- 0.06 to 1.08 +/- 0.10 micrograms/10(7) cells. In S37-bearing mice, Pro 23.3, 46.6, and 116.5 micrograms.ml-1 enhanced the malondialdehyde (MDA) formation in tumor and liver mitochondria and decreased MDA formation in liver mitochondria. These results suggested that the increases of Dox accumulation and MDA formation in tumor cells by Pro might be the reasons for synergistic effect of Pro on Dox cytotoxicity.