Growth Inhibition and Apoptosis Induced by Lupeol, a Dietary Triterpene, in Human Hepatocellular Carcinoma Cells
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概要
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Hepatocellular carcinoma (HCC) is the fifth most malignant tumor worldwide and is known to be resistant to conventional chemotherapy. New therapeutic strategies are urgently needed for treating HCC. Lup-20(29)-en-3H-ol (Lupeol), a novel dietary triterpene, is found in fruits, vegetables, and medicinal plants and possesses multiple bio-activities with very low toxicity. In the current study, we investigated its growth-inhibitory effects in HCC cell lines SMMC7721 and HepG2. In the in vitro studies, lupeol treatment alone caused decrease of cell viability in two HCC cell lines in a dose-dependent manner. It also induced apoptosis and caused cell accumulation in S phase. Further analysis revealed the induction of active caspase-3 and poly(ADP-ribose)polymerase (PARP) cleavage by lupeol treatment. In the in vivo studies, nude mice implanted with SMMC7721 cells subcutaneously were treated with lupeol three times a week and tumor development was significantly inhibited. We further investigated the combination anti-tumor effect of lupeol and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) in HCC, considering TRAIL treatment alone could not achieve high level of anti-tumor effect. The results demonstrated that lupeol could exert a combinational effect with TRAIL, resulting in chemosensitization of HCC. Our results suggested that lupeol alone or as an adjuvant to therapeutic agents could be developed as a potential agent for treating HCC.
著者
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WU Yan
Laboratory of Plant Molecular Biology, The Rockefeller University
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He Yan
Laboratory of Cellular and Molecular Tumor Immunology, Institute of Biology and Medical Sciences, So
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Liu Fen
Laboratory of Cellular and Molecular Tumor Immunology, Institute of Biology and Medical Sciences, So
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Zhang Lurong
Laboratory of Cellular and Molecular Tumor Immunology, Institute of Biology and Medical Sciences, So
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Hu Bo
Laboratory of Cellular and Molecular Tumor Immunology, Institute of Biology and Medical Sciences, So
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Zhang Yinsheng
Laboratory of Cellular and Molecular Tumor Immunology, Institute of Biology and Medical Sciences, So
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Li Yunsen
Laboratory of Cellular and Molecular Tumor Immunology, Institute of Biology and Medical Sciences, So
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Liu Haiyan
Laboratory of Cellular and Molecular Tumor Immunology, Institute of Biology and Medical Sciences, So
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Wu Yan
Laboratory Of Plant Molecular Biology The Rockefeller University
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Wu Yan
Laboratory of Cellular and Molecular Tumor Immunology, Institute of Biology and Medical Sciences, Soochow University
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Hu Bo
Laboratory of Cellular and Molecular Tumor Immunology, Institute of Biology and Medical Sciences, Soochow University
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Liu Fen
Laboratory of Cellular and Molecular Tumor Immunology, Institute of Biology and Medical Sciences, Soochow University
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He Yan
Laboratory of Cellular and Molecular Tumor Immunology, Institute of Biology and Medical Sciences, Soochow University
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Liu Haiyan
Laboratory of Cellular and Molecular Tumor Immunology, Institute of Biology and Medical Sciences, Soochow University
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Li Yunsen
Laboratory of Cellular and Molecular Tumor Immunology, Institute of Biology and Medical Sciences, Soochow University
関連論文
- Growth Inhibition and Apoptosis Induced by Lupeol, a Dietary Triterpene, in Human Hepatocellular Carcinoma Cells
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