Sinularin induces DNA damage, G2/M phase arrest, and apoptosis in human hepatocellular carcinoma cells

in Sciences Citation Index(SCI), 科學引文索引資料庫(SCI)
標題Sinularin induces DNA damage, G2/M phase arrest, and apoptosis in human hepatocellular carcinoma cells
出版類型SCI(Sciences Citation Index)
AuthorsTing-Wen Chung, 鍾婷雯, Shih-Chao Lin 林士超, Jui-Hsin Su 蘇瑞欣, Yu-Kuo Chen 陳與國, Chi-Chen Lin 林季千, & Hong-Lin Chan 詹鴻霖
出版日期2017 / 1

Sinularin isolated from the cultured soft coral Sinularia flexibilis has been reported to exert potent cytotoxic effects against particular types of cancer. This study was carried out to investigate the cytotoxic effects in sinularin-treated human hepatocellular carcinoma cells, HepG2, and to subsequently explore the underlying molecular mechanisms. The MTT (3-[4,5-dimethylthiazol-2-yl]-2, 5-diphenyl- tetrazolium bromide) method was used to evaluate the cytotoxicity of sinularin on HepG2 and Hep3B cell lines. Furthermore, the cell cycle distribution assay, apoptosis assay, and western blot analysis in vitro were used to explore the possible mechanisms of action. From the results of our study, cell viability was obviously inhibited by sinularin in a dose-dependent manner. In addition, our results suggested that sinularin triggered DNA damage and subsequently induced cell cycle G2/M arrest associated with up-regulation of p-ATM (Ser(1981)), p-Chk2 (Tyr(68)), p-cdc2 (Tyr(15)), and p53 coupled with increased expression of downstream proteins p21 and down-regulation of p-cdc25 (Ser(216)). Moreover, the results of the apoptosis assay and western blot analysis indicated that the cytotoxic activity could be related to mitochondrial apoptosis, characterized by decrease of Bcl-2 expression, disruption of mitochondrial membrane potential, and sequential activation of caspases and Poly (ADP-ribose) polymerase (PARP). This study reveals for the first time the anti-HCC activities of sinularin, the active compound isolated from the cultured soft coral Sinularia flexibilis. We believe that our results warrant further evaluation of sinularin as a new anti-HCC chemotherapeutic agent.

期刊名稱BMC Complementary and Alternative Medicine
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