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Updated: Apr 16, 2026
A Bioluminescent and Fluorescent Orthotopic Syngeneic Murine Model of Androgen-dependent and Castration-resistant Prostate Cancer
Published on: March 6, 2018
Nrf2 sensitizes prostate cancer cells to radiation via decreasing basal ROS levels
1Department of Urology, Shanghai Tenth People's Hospital, Tongji University, Shanghai, China.
Abstract:
Androgen deprivation therapy (ADT) was reported to lower basal ROS level in prostate cancer (PCa) and to sensitize PCa to radiation. We aimed to seek for the underlying molecular mechanism and to develop novel additive treatments to ADT in this regard. We simulated human androgen milieu in vitro and tested the ROS level in PCa cells undergoing ADT. We also tested the Nrf2 level in PCa cells with or without ADT. Genetic and pharmaceutical upregulation of Nrf2 was applied in vitro and in vivo in transgenic adenocarcinoma of the mouse prostate (TRAMP) mice with or without castration to investigate whether Nrf2 overexpression supplemented the effect of ADT in PCa. We first discovered that androgen deprivation increased basal ROS level in PCa cells with AR expression. We then found that genetic Nrf2 upregulation lowered basal ROS similar to ADT. Also, SFN sensitized PCa cell to radiation via upregulation of Nrf2. We then found that Nrf2 level in control TRAMP groups was lower than castration or SFN groups. The SFN treated TRAMP mice showed similar level of Nrf2 to castration. Genetic and pharmaceutical upregulation of Nrf2 lowered the ROS in PCa cells and sensitized PCa cells to radiation similar to ADT, implicating possible administration of SFN in place of ADT for PCa patients requiring radiotherapy.
Insights
Androgen deprivation therapy (ADT) increases reactive oxygen species (ROS) in prostate cancer (PCa) cells. Upregulating Nrf2, similar to ADT, reduces ROS and sensitizes PCa to radiation, suggesting SFN as a potential alternative treatment.
Area of Science:
- Oncology
- Molecular Biology
- Radiotherapy
Background:
- Androgen deprivation therapy (ADT) is a standard treatment for prostate cancer (PCa).
- ADT is known to lower reactive oxygen species (ROS) levels and sensitize PCa cells to radiation.
- The underlying molecular mechanisms and potential alternative treatments require further investigation.
Purpose of the Study:
- To elucidate the molecular mechanism by which ADT affects ROS levels in PCa.
- To investigate the role of Nrf2 in mediating the effects of ADT on ROS and radiosensitivity.
- To explore novel therapeutic strategies, including sulforaphane (SFN), as alternatives or adjuncts to ADT.
Main Methods:
- In vitro simulation of human androgen milieu and testing of ROS levels in PCa cells.
- Assessment of Nrf2 levels in PCa cells with and without ADT.
- In vitro and in vivo studies using genetic and pharmaceutical Nrf2 upregulation in TRAMP mice with or without castration.
- Evaluation of radiosensitization effects of Nrf2 modulation.
Main Results:
- Androgen deprivation increased basal ROS levels in AR-expressing PCa cells.
- Genetic Nrf2 upregulation mimicked ADT's effect by lowering basal ROS.
- Sulforaphane (SFN) sensitized PCa cells to radiation through Nrf2 upregulation.
- Nrf2 levels were lower in control TRAMP mice compared to castration or SFN-treated groups.
Conclusions:
- Nrf2 plays a crucial role in mediating the effects of ADT on ROS levels and radiosensitivity in PCa.
- Nrf2 upregulation, achieved through genetic or pharmaceutical means (like SFN), can replicate ADT's beneficial effects.
- SFN may be a viable alternative to ADT for PCa patients undergoing radiotherapy.
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