Selective antitumor activity of MKT-077, a delocalized lipophilic cation, on normal cells and cancer cells in vitro.
OBJECTIVE
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 (IC50) ranged from 1.7 to 14.3 microg/ml, with a mean +/- standard deviation (SD) of 8.4 +/- 4.6 microg/ml. The IC50 of fresh surgical spleen-cell specimens ranged from 0.34 microg/ml to >100 microg/ml in a 48 h incubation, with a mean +/- SD of 66.5 +/- 37.7 microg/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 microg/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.
Chiba
Y
Y
Department of Surgery, School of Medicine, Keio University, Tokyo, Japan.
Kubota
T
T
Watanabe
M
M
Otani
Y
Y
Teramoto
T
T
Matsumoto
Y
Y
Koya
K
K
Kitajima
M
M
D000970:Antineoplastic Agents / Q000494:pharmacology*; D003110:Colonic Neoplasms / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D020128:Inhibitory Concentration 50; D008297:Male; D010190:Pancreatic Neoplasms / Q000188:drug therapy*; D011725:Pyridines / Q000494:pharmacology*; D013154:Spleen / Q000187:drug effects* / Q000473:pathology; D013274:Stomach Neoplasms / Q000188:drug therapy*; D013844:Thiazoles / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D011725:Pyridines; D013844:Thiazoles; C097880:MKT 077