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Enzalutamide inhibits PEX10 function and sensitizes prostate cancer cells to ROS activators
Yuankang Feng1, Yu Zhang1, Hao Li1
1Department of Urology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China.
Abstract:
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.
Insights
Reactive oxygen species (ROS) play an unclear role in prostate cancer. Enzalutamide, combined with ROS activators, shows enhanced anti-tumor effects by targeting PEX10 expression regulated by the androgen receptor (AR).
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Reactive oxygen species (ROS) are implicated in cell damage, but their role in prostate cancer is not fully understood.
- Enzalutamide is a key anti-prostate cancer drug targeting the androgen receptor (AR).
- Understanding enzalutamide's mechanism and optimizing its application are critical for prostate cancer treatment.
Purpose of the Study:
- To investigate the role of PEX10 in prostate cancer cells and its regulation by ROS.
- To elucidate the mechanism by which enzalutamide affects PEX10 expression and its interaction with the AR.
- To explore a novel therapeutic strategy combining enzalutamide with ROS activators for prostate cancer.
Main Methods:
- Investigated PEX10 expression in prostate cancer cells under ROS activation.
- Assessed the effect of ROS activators on PEX10 levels and anti-tumor activity.
- Examined the regulation of PEX10 by the androgen receptor (AR) in conjunction with FOXA1.
- Evaluated the synergistic anti-tumor effects of enzalutamide combined with ROS activators (ML210, RSL3).
Main Results:
- PEX10 is induced by ROS activators but reduces ROS levels, potentially counteracting anti-tumor effects.
- Androgen receptor (AR), with FOXA1, enhances PEX10 expression.
- Enzalutamide inhibits PEX10 by blocking AR function.
- Enzalutamide synergizes with ROS activators ML210 or RSL3, enhancing anti-tumor efficacy and sensitizing cells to ROS activators.
Conclusions:
- PEX10 plays a role in modulating ROS levels within prostate cancer cells.
- Enzalutamide's inhibition of AR-mediated PEX10 expression offers a new therapeutic avenue.
- Combining enzalutamide with ROS activators presents a promising strategy for enhanced prostate cancer treatment.
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