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

BMC Complementary and Alternative Medicine

Research Article

Yu-Kuo Chen¹  Ting-Wen Chung²  Hong-Lin Chan²  Chi-Chien Lin³  Shih-Chao Lin⁴  Jui-Hsin Su⁵ 

[1] Department of Food Science, National Pingtung University of Science and Technology, Pingtung, Taiwan;Institute of Bioinformatics and Structural Biology and Department of Medical Sciences, National Tsing Hua University, Hsinchu, Taiwan;Institute of Biomedical Science, National Chung-Hsing University, Taichung, Taiwan;Department of Biotechnology, Asia University, Taichung, Taiwan;Department of Medical Research, China Medical University Hospital, Taichung, Taiwan;Ph.D. Program in Medical Biotechnology, National Chung Hsing University, Taichung, Taiwan;SRI international, Harrisonburg, VA, USA;Taiwan Coral Research Center, National Museum of Marine Biology & Aquarium, Pingtung, Taiwan;

关键词: Sinularin;    Sinularia flexibilis;    Hepatocellular carcinoma;    G2/M;    Apoptosis;    DNA damage;   

DOI  :  10.1186/s12906-017-1583-9

 received in 2016-10-10, accepted in 2017-01-14,  发布年份 2017

来源: Springer

【 摘 要 】

BackgroundSinularin 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.MethodsTheMTT (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.ResultsFrom 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).ConclusionsThis 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.

【 授权许可】

CC BY   
© The Author(s). 2017