Enzalutamide inhibits PEX10 function and sensitizes prostate cancer cells to ROS activators

作者：Yuankang Feng, Yu Zhang, Hao Li, Tao Wang, Fubo Lu, Ruoyang Liu, Guoqing Xie, Liang Song, Budeng Huang, Xiang Li, Yinghui Ding, Jinjian Yang, Zhankui Jia, Zhenlin Huang · 发表于：Cell Death and Disease · 年份：2024 · DOI：10.1038/s41419-024-06937-7 · 被引用次数：7 · 研究领域：Prostate Cancer Treatment and Research、Cancer, Lipids, and Metabolism、Mass Spectrometry Techniques and Applications

Sharply increased reactive oxygen species (ROS) are thought to induce oxidative stress, damage cell structure and cause cell death; however, its role in prostate cancer remains unclear. Enzalutamide is a widely used anti-prostate cancer drug that antagonizes androgen binding with its receptor. Further exploration of the mechanism and potential application strategies of enzalutamide is crucial for the treatment of prostate cancer. Here, we confirmed PEX10 can be induced by ROS activators while reduce ROS level in prostate cancer cells, which weakened the anti-tumor effect of ROS activators. The androgen receptor (AR) can promote the expression of PEX10 by acting as an enhancer in cooperation with FOXA1. The anti-tumor drug enzalutamide inhibits PEX10 by inhibiting the function of AR, and synergize with ROS activators ML210 or RSL3 to produce a stronger anti-tumor effect, thereby sensitizing cells to ROS activators. This study reveals a previously unrecognized function of enzalutamide and AR by regulating PEX10 and suggests a new strategy of enzalutamide application in prostate cancer treatment.