Wu Jung-Ju, Omar Hany A, Lee Ying-Ray, Teng Yen-Ni, Chen Pin-Shern, Chen Yu-Chung, Huang Hsiao-Shan, Lee Kuan-Han, Hung Jui-Hsiang
Department of Chinese Medicine, Chiayi Christian Hospital, Chiayi, Taiwan.
Department of Pharmacology, Faculty of Pharmacy, Beni-Suef University, Beni-Suef, Egypt; Sharjah Institute For Medical Research, Department of Pharmacology, College of Pharmacy, University of Sharjah, Sharjah, United Arab Emirates.
Eur J Pharmacol. 2015 Sep 5;762:449-58. doi: 10.1016/j.ejphar.2015.06.032. Epub 2015 Jun 20.
Shogaols are a group of the active constituents of ginger that have been identified to have various biological activities. The aim of the current study was to investigate the antitumor activity of 6-shogaol in hepatocellular carcinoma (HCC) and the possible involvement of reactive oxygen species as a putative mechanism of action. HCC cell lines, HepG2 and Huh-7, were used to study the in vitro anti-cancer activity of 6-shogaol via the application of various molecular biology techniques. Results showed that 6-shogaol effectively inhibited the cell viability, caused cell cycle arrest at G2/M phase and induced apoptosis in HCC cells as indicated by MTT assay, DAPI nuclear staining, annexin V assay, cell cycle analysis, and activation of caspase-3. Western blot analysis revealed the ability of 6-shogaol to target cancer survival signaling pathways mediated by mitogen-activated protein kinase (MAPK), 5' AMP-activated protein kinase (AMPK) and Akt. In addition, 6-Shogaol induced alteration of cyclin proteins expression and caused cleavage of protein kinase C delta. Furthermore, 6-Shogaol was able to induce the production of reactive oxygen species and endoplasmic reticulum (ER) stress-associated proteins and the consequent activation of autophagy in HepG2 cells. Taken together, the current study highlights evidences that 6-shogaol induces apoptosis, modulates cyclins expression and targets cancer survival signaling pathways in HCC cell lines, at least in part, via the production of reactive oxygen species. These findings support 6-shogaol's clinical promise as a potential candidate for HCC therapy.
姜辣素是生姜中的一组活性成分，已被确定具有多种生物活性。本研究的目的是探讨6-姜辣素对肝细胞癌（HCC）的抗肿瘤活性以及活性氧作为一种推定作用机制的可能参与情况。通过应用各种分子生物学技术，使用HCC细胞系HepG2和Huh-7来研究6-姜辣素的体外抗癌活性。结果表明，MTT法、DAPI核染色、膜联蛋白V检测、细胞周期分析和caspase-3激活显示，6-姜辣素有效抑制细胞活力，使细胞周期停滞在G2/M期并诱导HCC细胞凋亡。蛋白质免疫印迹分析显示，6-姜辣素能够靶向由丝裂原活化蛋白激酶（MAPK）、5'-腺苷单磷酸活化蛋白激酶（AMPK）和Akt介导的癌症生存信号通路。此外，6-姜辣素诱导细胞周期蛋白表达改变并导致蛋白激酶Cδ裂解。此外，6-姜辣素能够诱导活性氧的产生以及内质网（ER）应激相关蛋白的产生，并随之激活HepG2细胞中的自噬。综上所述，本研究突出了以下证据：6-姜辣素至少部分通过活性氧的产生诱导HCC细胞系凋亡、调节细胞周期蛋白表达并靶向癌症生存信号通路。这些发现支持6-姜辣素作为HCC治疗潜在候选药物的临床前景。
