title: Oxidative stress and androgen receptor signaling in the development and progression of castration-resistant prostate cancer.
abstract: Aberrant androgen receptor (AR) signaling plays a critical role in androgen-dependent prostate cancer (PCa), as well as in castration-resistant PCa (CRPC). Oxidative stress seems to contribute to the tumorigenesis and progression of PCa, as well as the development of CRPC, via activation of AR signaling. This notion is supported by the fact that there is an aberrant or improper regulation of the redox status in these disorders. Additionally, androgen-deprivation-induced oxidative stress seems to be involved in the pathogenesis of several disorders caused by androgen-deprivation therapy (ADT), including osteoporosis, neurodegenerative disease, and cardiovascular disease. Oxidative stress can be suppressed with antioxidants or via a reduction in reactive oxygen species production. Thus, developing new therapeutic agents that reduce oxidative stress might be useful in preventing the conversion of androgen-dependent PCa into CRPC, as well as reducing the adverse effects associated with ADT. The objective of this review is to provide an overview regarding the relationship between oxidative stress and AR signaling in the context of PCa and especially CRPC. Additionally, we discuss the potential use of antioxidant therapies in the treatment of PCa.
authors.affiliation: Department of Urology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. shiota@uro.med.kyushu-u.ac.jp
authors.forename: Masaki
authors.initials: M
authors.lastname: Shiota
authors.forename: Akira
authors.initials: A
authors.lastname: Yokomizo
authors.forename: Seiji
authors.initials: S
authors.lastname: Naito
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology / Q000627:therapeutic use; D000726:Androgen Antagonists / Q000009:adverse effects / Q000494:pharmacology; D000728:Androgens / Q000096:biosynthesis / Q000172:deficiency / Q000494:pharmacology; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology / Q000627:therapeutic use; D002277:Carcinoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D016207:Cytokines / Q000378:metabolism; D018450:Disease Progression; D015870:Gene Expression; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D008297:Male; D051379:Mice; D009154:Mutation; D009919:Orchiectomy; D018384:Oxidative Stress; D011467:Prostate / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism*; D011944:Receptors, Androgen / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: C410798:AR protein, human; D000726:Androgen Antagonists; D000728:Androgens; D000975:Antioxidants; D016207:Cytokines; D036341:Intercellular Signaling Peptides and Proteins; D020033:Protein Isoforms; D011944:Receptors, Androgen; D000111:Acetylcysteine