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 (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.
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 humancancer 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.
Authors: Aikaterini Rousaki; Yoshinari Miyata; Umesh K Jinwal; Chad A Dickey; Jason E Gestwicki; Erik R P Zuiderweg Journal: J Mol Biol Date: 2011-06-25 Impact factor: 5.469
Authors: Yoshinari Miyata; Xiaokai Li; Hsiu-Fang Lee; Umesh K Jinwal; Sharan R Srinivasan; Sandlin P Seguin; Zapporah T Young; Jeffrey L Brodsky; Chad A Dickey; Duxin Sun; Jason E Gestwicki Journal: ACS Chem Neurosci Date: 2013-03-20 Impact factor: 4.418
Authors: Ayman N Abunimer; Heba Mohammed; Katherine L Cook; David R Soto-Pantoja; Maria Mercedes Campos; Mones S Abu-Asab Journal: Ultrastruct Pathol Date: 2018-02-08 Impact factor: 1.094
Authors: Barbara Bachowska; Julia Kazmierczak-Baranska; Marcin Cieslak; Barbara Nawrot; Dorota Szczęsna; Joanna Skalik; Piotr Bałczewski Journal: ChemistryOpen Date: 2012-02-17 Impact factor: 2.911