Equol inhibits proliferation of human gastric carcinoma cells via modulating Akt pathway

作     者：Zhi-Ping Yang Yan Zhao Fang Huang Jie Chen Ya-Hong Yao Jun Li Xiao-Nan Wu 

作者机构：Public Health CollegeFujian Medical University The First Affiliated Hospital of Xiamen University 

出 版 物：《World Journal of Gastroenterology》 (世界胃肠病学杂志（英文版）)

年 卷 期：2015年第21卷第36期

页      面：10385-10399页

核心收录：

学科分类：1002[医学-临床医学] 100214[医学-肿瘤学] 10[医学] 

基　　金：Supported by Special Project on the Integration of Industry Education and Research of Fujian Province China No.2012N0014 

主　　题：Equol Apoptosis Chemoprevention Gastric cancer G0/ 

摘      要：AIM: To investigate the anti-tumor effects of equol in gastric cancer cells and the underlying molecular ***: MGC-803 cells were employed for in vitro experiments in this study. Cells were treated with control(vehicle,0.1% DMSO) or equol under specified dose titration or time courses. Cell viability was examined by MTS assay,and the levels of Ki67 were determined by q PCR and immunofluorescent assay. Changes in cell cycle distribution and apoptosis rate were detected by flow cytometry. The m RNA expression of cyclin E1 and P21WAF1 was determined by q PCR. The protein levels of cell cycle regulators,PARP and Caspase-3 cleavage,and the phosphorylation of Akt were examined by Western blot. In addition,to characterize the role of elevated Akt activation in the anti-tumor effect exerted by equol,Ly294002,a PI3K/AKT pathway inhibitor,was used to pretreat MGC-803 cells. RESULTS: Equol(5,10,20,40,or 80 μmol/L) inhibited viability of MGC-803 cells in a dose- and timedependent manner after treatment for 24,36,or 48 h(P 0.05 for all). Equol also decreased the m RNA(P 0.05 for 12 and 24 h treatment) and protein levels of Ki67. Equol treatment significantly induced G0/G1 cell cycle arrest(P 0.05),with the percentages of G0/G1 cells of 32.23% ± 3.62%,36.31% ± 0.24%,45.58% ± 2.29%,and 65.10% ± 2.04% for equol(0,10,20,or 30 μmol/L) treatment,respectively,accompanied by a significant decrease of CDK2/4(P 0.05 for 24 and 48 h treatment) and Cyclin D1/Cyclin E1(P 0.05),and an increased level of P21WAF1(P 0.05). A marked increase of apoptosis was observed,with the percentages of apoptotic cells of 5.01% ± 0.91%,14.57% ± 0.99%,37.40% ± 0.58%,and 38.46% ± 2.01% for equol(0,5,10,or 20 μmol/L) treatment,respectively,accompanied by increased levels of cleaved PARP and caspase-3. In addition,we found that equol treatment increased P-Akt(Ser473 and Thr308) at 12 and 24 h compared to vehicle-treated control; longer treatment for 48 h decreased P-Akt(Ser473 and Thr308)