Antitumor activity of delocalized lipophilic cation, MKT-077 in human carcinomas obtained from fresh surgical specimens

Abstract

Background. MKT-077, a delocalized lipophilic cation, accumulates in mitochondria according to the negative potential inside the mitochondria and exerts cytotoxicity. We investigated the antitumor activity and spectrum of MKT-077 in fresh surgical specimens.

Methods. Single cell suspensions of fresh surgical specimens obtained from patients with gastric, colon, and hepatocellular carcinoma were treated with MKT-077 at a cutoff concentration of 30 μg/ml. Cell viability was detected by 3-(4,5-dimethylthiazol-2yl)-2,5-diphenyl-2H tetrazolium bromide (MTT) assay.

Results. When the cutoff concentration was 30 μg/ml, the efficacy rates (sensitive cases/evaluated cases in percent) of MKT-077 were 52.6% for gastric cancer, 77.8% for colon cancer, and 35.7% for hepatocellular carcinoma, resulting in an overall efficacy rate of 52.4% (22/42). This was higher than the rates for other agents, including mitomycin C, doxorubicin, 5-fluorouracil, and cisplatin. The antitumor spectrum of MKT-077 was correlated with that of doxorubicin, while the antitumor spectra of mitomycin C, 5-fluorouracil, and cisplatin were completely independent of that of MKT-077.

Conclusion. Since MKT-077 seemed to have a different antitumor spectrum from that of the conventionally available agents, further investigation should be conducted, including studies of the combined effect of MKT-077 and other antitumor agents.