| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2001: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 2000: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1999: ¥1,500,000 (Direct Cost: ¥1,500,000)
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| Research Abstract |
Delocalized lipophilic cation (DLC) is a kind of antitumor agent, which selectively accumulated in the mitochondria of tumor cells. MKT-077 was selected from 100,000 candidate DLC compounds based upon its high water-solubility, stability and selective cytotoxicity on tumor cells. The selective cytotoxicity of MKT-077 was evaluated using cultured human cancer cell lines, fresh surgical specimens and human tumor xenografts serially grown in nude mouse. [Materials and Methods] MKY-077 was tested using 8 human cancer cell lines, 51 fresh surgical specimens (27 gastric cancer, 10 colon cancer, 14 hepatocellular carcinoma), and cominedly resected 10 human spleens. One gastric (St4), 3 colon (Co-4, HT-29, LS174T), and pancreatic (CRI1420) carcinoma xenografts were transplanted into nude mouse and MKT-077 was administered for 7 days using osmotic micro-pump. [Result and Discussion] The cytotoxicity of MKT-077 in vitro depended on time x concentration, and 50% inhibitory concentrations ranged 1.7-14.3 ^g/ml. The gastric cancer specimens were sensitive to MKT-077 in a time x concentration manner, while the spleen cells obtained from the same host were resistant to this agent. When in vivo cytotoxicity of MKT-077 was tested, the continuous administration method was most effective in the same totally administered doses, and 3 of 5 strains were assessed to be sensitive to this agents. MKT-077 has a new mode of action, which selectively accumulates in tumor mitochondria, and elucidated its antitumor activity. A further clinical trial was warranted.
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