Selective antitumor activity of MKT-077, a delocalized lipophilic cation, on normal cells and cancer cells in vitro
✍ Scribed by Chiba, Yohei; Kubota, Tetsuro; Watanabe, Masahiko; Otani, Yoshihide; Teramoto, Tatsuo; Matsumoto, Yoichi; Koya, Keizo; Kitajima, Masaki
- Publisher
- John Wiley and Sons
- Year
- 1998
- Tongue
- English
- Weight
- 125 KB
- Volume
- 69
- Category
- Article
- ISSN
- 0022-4790
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✦ Synopsis
Background and Objectives: 1-Ethyl-2-{[3-ethyl-5-(3-methylbenzothiazolin-2-yliden)]-4-oxothiazolidin-2-ylidenemethyl}pyridium chloride (MKT-077, formerly known as FJ776), a delocalized lipophilic cation, is known to accumulate in the mitochondria, according to the negative potential inside the mitochondria, and exert its cytotoxicity. Methods: The single-cell suspensions of human cancer cell lines, human spleen cells, and fresh cancer specimens obtained from patients with gastric carcinoma were used for the 3-(4,5-dimethylthiazol-2yl)-2,5-diphenyl-2H tetrazolium bromide (MTT) assay.
Results:
The antitumor activity of MKT-077 was dose and concentration related, and 50% inhibitory concentrations (IC 50 ) ranged from 1.7 to 14.3 g/ml, with a mean ± standard deviation (SD) of 8.4 ± 4.6 g/ml. The IC 50 of fresh surgical spleen-cell specimens ranged from 0.34 g/ml to >100 g/ml in a 48 h incubation, with a mean ± SD of 66.5 ± 37.7 g/ml. When the antitumor activity of MKT-077 was compared between gastric cancer cells and spleen cells obtained from the same patient, the concentration-dependent antitumor activity of this agent was obvious in the cancer cells, while no significant cytotoxicity was observed in the spleen cells. The fresh surgical specimens of gastric cancer showed higher sensitivity to MKT-077 than did spleen cells at a concentration of 30 g/ml, with a statistically significant difference at P < 0.05. Conclusions: The selective antitumor activity of MKT-077 was confirmed using fresh surgical specimens and warrants further investigation.