| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2005: ¥2,200,000 (Direct Cost: ¥2,200,000)
Fiscal Year 2004: ¥1,300,000 (Direct Cost: ¥1,300,000)
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| Research Abstract |
Aims : Matrix metalloproteinases (MMPs) can degrade variety of extracellular matrices (ECM) including collagen, laminin, proteoglycan and so on. The destruction of ECM components during cancer invasion and metastasis is well recognized. Recently, citrus flavonoids including nobiletin are known to suppress MMPs production and to exert anticancer activity in vitro. We have already reported the suppression of peritoneal nodule formation of gastric cancer cells in peritoneal dissemination model of SCID mouse (Jpn J Cancer Res, 92 : 1322-1328, 2001). Therefore, we plan to figure out the anti-tumor effects of nobiletin on gastric cancer cells from several aspects. Materials and methods : Human gastric cancer cell lines, TMK-1, MKN-45, MKN-74 and KATO-III were used for this study. The direct cytotoxicity of nobiletin was examined by MTT assay, the induction of apoptosis was investigated by TUNEL method and the effect on cell cycle was measured by DNA histogram using flow cytometry. Results : Nobiletin significantly showed the direct cytotoxicity on the four cell lines examined. Apoptosis was observed and the block of cell cycle was evident at G1 phase by nobiletin. Conclusion : The control of ECM destruction, direct cytotoxicity, the induction of apoptosis and G1 arrest on gastric cancer cells caused by nobiletin, represent a potential strategy for the treatment of gastric cancer.
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