Androgens induce oxidative stress and radiation resistance in prostate cancer cells though NADPH oxidase.
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.
Lu
J P
JP
Department of Surgery, Faculty of Health Sciences, McMaster University, Hamilton, Ontario, Canada.
Monardo
L
L
Bryskin
I
I
Hou
Z F
ZF
Trachtenberg
J
J
Wilson
B C
BC
Pinthus
J H
JH
D000098:Acetophenones / Q000494:pharmacology; D000111:Acetylcysteine / Q000494:pharmacology; D000726:Androgen Antagonists / Q000494:pharmacology*; D000728:Androgens / Q000494:pharmacology*; D000813:Anilides / Q000494:pharmacology; D000818:Animals; D045744:Cell Line, Tumor / Q000528:radiation effects; D006801:Humans; D008297:Male; D008562:Membrane Glycoproteins / Q000096:biosynthesis; D015741:Metribolone / Q000494:pharmacology; D051379:Mice; D000074662:NADPH Oxidase 2; D000074663:NADPH Oxidase 4; D019255:NADPH Oxidases / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000378:metabolism / Q000502:physiology*; D009368:Neoplasm Transplantation; D009570:Nitriles / Q000494:pharmacology; D009861:Onium Compounds / Q000494:pharmacology; D018384:Oxidative Stress / Q000187:drug effects*; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000532:radiotherapy; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D014105:Tosyl Compounds / Q000494:pharmacology
D000098:Acetophenones; D000726:Androgen Antagonists; D000728:Androgens; D000813:Anilides; D008562:Membrane Glycoproteins; D009570:Nitriles; D009861:Onium Compounds; D011838:Radiation-Sensitizing Agents; D017382:Reactive Oxygen Species; D014105:Tosyl Compounds; D015741:Metribolone; C007517:diphenyleneiodonium; C053541:bicalutamide; C056165:acetovanillone; C056558:CYBB protein, human; D000074662:NADPH Oxidase 2; D000074663:NADPH Oxidase 4; D019255:NADPH Oxidases; C498910:NOX4 protein, human; C086986:CYBA protein, human; D000111:Acetylcysteine