| Summary: | 碩士 === 中國醫藥大學 === 臨床醫學研究所碩士班 === 98 === Prostate cancer (CaP) is one of the most prevalent cancers worldwide and the incidence and mortality rates has been rapidly increasing in Taiwan in the recent years. Therefore, it is important to develop anti-cancer therapy. In this study, KHC-4 was identified from 2-phenyl-4-quionolone derivatives and as a cancer chemotherapeutic agents that interfere with tubulin/microtubule function. In this study, we have identified the anticancer mechanisms of KHC-4 in human prostate cancer cell line, DU145. In our results, KHC-4 inhibited cell proliferation and induced cytotoxicity effect in castration-resistant prostate cancer DU145 cells. The IC50 value was 0.1 μM. Cell cycle analysis demonstrated that KHC-4 caused G2/M arrest and a subsequent increase of Sub-G1 population. Furthermore, KHC-4 up-regulated p21, p27 and p53 in a time- and a concentration-dependent manner. The exposure of cells to KHC-4 caused Cdk1/cyclin B1 complex activity which leaded to cell cycle arrest. Inaddition, KHC-4 suppressed the anti-apoptotic protein levels of Bcl-2, Bcl-xL, up-regulated the Bax and induced apoptosis by mitochondrial-dependent pathway. KHC-4 also induced releasing of cytochrome c and AIF. Additionally, KHC-4 induced the activation of several caspases, including caspase -8 and -9. In addition, KHC-4 inhibited MMP-2 and MMP-9 protein activities to prohibit tumor cells metastasis. We concluded that the antitumor effects of KHC-4 in DU145 cells include the mitotic arrest, induction of apoptosis and against tumor invasion.
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