Heat shock protein 27 mediates the effect of 1,3,5-trihydroxy-13,13-dimethyl-2H-pyran [7,6-b] xanthone on mitochondrial apoptosis in hepatocellular carcinoma
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摘要Hepatocellular carcinoma (HCC) is a global public health problem which causes approximately 500000 deaths annually. Considering that the limited therapeutic options for HCC, novel therapeutic targets and drugs are urgently needed. In this study, we discovered that 1,3,5-trihydroxy-13,13-dimethyl-2H-pyran [7,6-b] xanthone (TDP), isolated from the traditional Chinese medicinal herb, Garcinia oblongifolia, effectively inhibited cell growth and induced the caspase-dependent mitochondrial apoptosis in HCC. A two-dimensional gel electrophoresis and mass spectrometry-based comparative proteomics were performed to find the molecular targets of TDP in HCC cells. Eighteen proteins were identified as differently expressed, with Hsp27 protein being one of the most significantly down-regulated proteins induced by TDP. In addition, the following gain- and loss-of-function studies indicated that Hsp27 mediates mitochondrial apoptosis induced by TDP. Furthermore, a nude mice model also demonstrated the suppressive effect of TDP on HCC. Our study suggests that TDP plays apoptosis-inducing roles by strongly suppressing the Hsp27 expression that is specifically associated with the mitochondrial death of the caspase-dependent pathway. In conclusion, TOP may be a potential anti-cancer drug candidate, especially to cancers with an abnormally high expression of Hsp27. (C) 2012 Elsevier B.V. All rights reserved.
著者Fu WM, Zhang JF, Wang H, Xi ZC, Wang WM, Zhuang P, Zhu X, Chen SC, Chang TM, Leung KS, Lu G, Xu HX, Kung HF
期刊名稱Journal of Proteomics
出版年份2012
月份8
日期3
卷號75
期次15
出版社ELSEVIER SCIENCE BV
頁次4833 - 4843
國際標準期刊號1874-3919
語言英式英語
關鍵詞1,3,5-trihydroxy-13,13-dimethyl-2H-pyran [7,6-b] xanthone; Hepatocellular carcinoma; Hsp27; Mitochondrial apoptosis
Web of Science 學科類別Biochemical Research Methods; BIOCHEMICAL RESEARCH METHODS; Biochemistry & Molecular Biology

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