Free Radical Biology & Medicine, 2015, 86:209-218.

Genistein induces apoptosis by stabilizing intracellular p53 protein through an APE1-mediated pathway

Jianwu Zhu, Chong Zhang, Yi Qing, et al

Cancer Center, Research Institute of Surgery, Daping Hospital, Third Military Medical University, Chongqing 400042, People's Republic of China

Genistein (GEN) has been previously shown to have a proapoptotic effect on cancer cells through a p53-dependent pathway, the mechanism of which remains unclear. One of its intracellular targets, APE1, protects against apoptosis under genotoxic stress and interacts with p53. In this current study, we explored the mechanism of the proapoptotic effect of GEN by examining the APE1-p53 protein-protein interaction. We initially showed that the p53 protein level was elevated in GEN-treated human non-small lung cancer A549 cells and cervical cancer HeLa cells. By examining both protein synthesis and degradation, we found that GEN enhances p53 intracellular stability by interfering with the interaction of APE1 and p53, which provided a plausible explanation for how GEN initiates apoptosis. Furthermore, we found that the interaction between APE1 and p53 is important for the degradation of p53 and is dependent on the redox domain of APE1 by utilizing the redox domain mutant APE1 C65A. Our data suggest that the degradation of wild-type p53 is blocked when the redox domain of APE1 is masked or interrupted. Based on this evidence, we hereby report a novel mechanism of p53 degradation through an APE1-mediated, redox-dependent pathway.

美国《自由基生物学与医学》, 2015, 86:209-218.

金雀异黄素通过 APE1-介导的途径使细胞内 p53 蛋白稳定从而诱导细胞凋亡
祝建武，张冲，等
第三军医大学大坪医院外科研究所癌症中心，重庆400042，中华人民共和国