Androgens induce oxidative stress and radiation resistance in prostate cancer cells though NADPH oxidase

Abstract

Androgen deprivation therapy (ADT) facilitates the response of prostate cancer (PC) to radiation. Androgens have been shown to induce elevated basal levels of reactive oxygen species (ROS) in PC, leading to adaptation to radiation-induced cytotoxic oxidative stress. Here, we show that androgens increase the expression of p22 phox and gp91 phox subunits of NADPH oxidase (NOX) and ROS production by NOX2 and NOX4 in PC. Pre-radiation treatment of 22Rv1 human PC cells with NOX inhibitors sensitize the cells to radiation similarly to ADT, suggesting that their future usage may spare the need for adjuvant ADT in PC patients undergoing radiation.

Activation of Androgen Receptor, Lipogenesis, and Oxidative Stress Converged by SREBP-1 Is Responsible for Regulating Growth and Progression of Prostate Cancer Cells

“…ROS and Nox (a ROS generator), have been reported to regulate cell proliferation, progression, metastasis and radiation resistance of prostate cancer cells (33–35). Our cDNA microarray data revealed that Nox5 was up-regulated in overexpressing SREBP-1 prostate cancer cells compared to control cells (unpublished data).…”

NADPH oxidase subunit 4 mediates cycling hypoxia-promoted radiation resistance in glioblastoma multiforme

“…In a recent study, Lu et al demonstrate that Nox4 is involved in androgen-induced oxidative stress and radiation resistance in prostate cancer cells [42]. This androgen-induced ROS production and radioresistance in prostate cancer cells are mediated via Nox2 and Nox4, and the inhibition of Nox by apocynin can sensitize in vitro tumor cells to radiation.…”

NADPH Oxidase-Mediated Redox Signaling: Roles in Cellular Stress Response, Stress Tolerance, and Tissue Repair

“…Thus, manipulating the intracellular redox state might potentially serve as a strategy for increasing their sensitivity to chemotherapeutic drugs or irradiation. In prostate cancer cells, it has been shown that androgen can induce elevated basal levels of ROS, thereby resulting in adaptation to radiation-induced cytotoxic stress (Lu et al, 2010). It is noteworthy that androgen-induced ROS generation in prostate cancer cells was dependent on Nox2 and Nox4; preradiation treatment with Nox inhibitors sensitized the cells to radiation-induced cytotoxicity (Lu et al, 2010).…”

“…In prostate cancer cells, it has been shown that androgen can induce elevated basal levels of ROS, thereby resulting in adaptation to radiation-induced cytotoxic stress (Lu et al, 2010). It is noteworthy that androgen-induced ROS generation in prostate cancer cells was dependent on Nox2 and Nox4; preradiation treatment with Nox inhibitors sensitized the cells to radiation-induced cytotoxicity (Lu et al, 2010). In another study, stable expression of the constitutively active mutant V12-H-Ras in virus transformed human lung cells dramatically increased intracellular production of superoxide via activation of Nox and induced resistance to TNF-␣-mediated apoptosis (Liu et al, 2001).…”