Mechanism of Sensitizing Effect of PPARα Activation on Epigallocatechin-3-gallate (EGCG) in Cancer Cells
LUO Judong1,2, XUE Jiao1, GE Xin1, GE Yangyang1, CAO Jianping1, ZHANG Shuyu1
1. School of Radiation Medicine and Protection; Jiangsu Provincial Key Laboratory of Radiation Medicine and Protection, Soochow University, Suzhou 215123, Jiangsu Province, China;2. Department of Radiotherapy, Changzhou Tumor Hospital, Soochow University, Changzhou 213001, Jiangsu Province, China
Abstract：Whether epigallocatechin-3-gallate (EGCG) regulates the expression of PPARα and the effect of PPARα on EGCG sensitivity. Firstly, CCK-8 kit was used to detect cell viability. Western blotting and real-time PCR was used to measure the protein and mRNA level, respectively. PPARα agonist clofibrate and inhibitor GW6471 were used to alter PPARα expression. Luciferase reporter system and chromatin immunoprecipitation (ChIP) were used to investigate the effect of PPARα on HO-1 expression. EGCG inhibits the viability of cancer cell in a dose-dependent manner. When cancer cells were exposed to EGCG, the expression of PPARα was increased at the protein level in a dose-dependent manner. The PPARα agonist clofibrate attenuated heme oxygenase (HO-1) induction and sensitized cancer cells to EGCG-induced cell death. However, the PPARα inhibitor GW6471 increased HO-1 expression. In vivo chromatin immunoprecipitation (ChIP) confirmed that PPARα interacts with the peroxisome proliferator-responsive sequence of the HO-1 promoter. These results indicate that PPARα is a direct negative regulator of HO-1 activation by EGCG and confers cell susceptibility to EGCG.
罗居东;薛姣;葛欣;葛杨杨;曹建平;张舒羽. PPARα活化增加肿瘤细胞对EGCG的敏感性的机制[J]. , 2013, 31(27): 21-26.
LUO Judong;XUE Jiao;GE Xin;GE Yangyang;CAO Jianping;ZHANG Shuyu. Mechanism of Sensitizing Effect of PPARα Activation on Epigallocatechin-3-gallate (EGCG) in Cancer Cells. , 2013, 31(27): 21-26.