2001 Fiscal Year Final Research Report Summary
Newly developed lipophilic cation (MKT-077) which elucidates its antitumor activity though the selective accumulation in tumor mitochondria
| Project/Area Number |
11671182
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
General surgery
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| Research Institution | Keio University |
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Principal Investigator |
KUBOTA Tatsuro Keio Univ., School of Medicine, Associate Professor, 医学部, 助教授 (00118944)
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| Project Period (FY) |
1999 – 2001
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| Keywords | mitochondria / lodacyanine / delocalization / cation / cytotoxicity |
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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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[Publications] Chiba, Y., Kubota, T., Watanabe, M., Otani, Y., Kitajima, M.: "Antitumor activity of delocalized lipophilic cation, MKT-077 in human carcinomas obtained from fresh surgical specimens"International Journal of Clinical Oncology. 4. 65-68 (1999)
Description
「研究成果報告書概要(和文)」より
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[Publications] Chiba, Y, Kubota, I, Watanabe, M., Otani, Y, and Kitajima, M: "Antitumor activity of delocalized lipophilic cation, MKT-077 in human carcinomas obtained from fresh surgical specimens"International Journal of Clinical Oncology. 4. 65-68 (1999)
Description
「研究成果報告書概要(欧文)」より
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