779 ANTIOXIDANT THERAPY ALLEVIATES OXIDATIVE STRESS BY ANDROGEN DEPRIVATION AND PREVENTS CONVERSION FROM ANDROGEN-DEPENDENT TO CASTRATION-RESISTANT PROSTATE CANCER

Abstract

You have accessJournal of UrologyProstate Cancer: Basic Research IV1 Apr 2012779 ANTIOXIDANT THERAPY ALLEVIATES OXIDATIVE STRESS BY ANDROGEN DEPRIVATION AND PREVENTS CONVERSION FROM ANDROGEN-DEPENDENT TO CASTRATION-RESISTANT PROSTATE CANCER Masaki Shiota, YooHyun Song, Ario Takeuchi, Akira Yokomizo, Eiji Kashiwagi, Kentaro Kuroiwa, Katsunori Tatsugami, Takeshi Uchiumi, Yoshinao Oda, and Seiji Naito Masaki ShiotaMasaki Shiota Fukuoka, Japan More articles by this author , YooHyun SongYooHyun Song Fukuoka, Japan More articles by this author , Ario TakeuchiArio Takeuchi Fukuoka, Japan More articles by this author , Akira YokomizoAkira Yokomizo Fukuoka, Japan More articles by this author , Eiji KashiwagiEiji Kashiwagi Fukuoka, Japan More articles by this author , Kentaro KuroiwaKentaro Kuroiwa Fukuoka, Japan More articles by this author , Katsunori TatsugamiKatsunori Tatsugami Fukuoka, Japan More articles by this author , Takeshi UchiumiTakeshi Uchiumi Fukuoka, Japan More articles by this author , Yoshinao OdaYoshinao Oda Fukuoka, Japan More articles by this author , and Seiji NaitoSeiji Naito Fukuoka, Japan More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2012.02.867AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES We previously reported that oxidative stress induced by androgen deprivation therapy (ADT) played the important role in the progression of prostate cancer (PCa) from androgen-dependent to castration-resistant PCa (CRPC). (Oncogene 29:237, 2010, Endocr Relat Cancer 18:505, 2011). We aimed to elucidate the state and the role of oxidative stress induced by ADT and the possibility of antioxidant therapy in human PCa. METHODS Oxidative stress marker 4-hydroxy-2-nonenal histidine adduct (4-HNE) staining, and oxidative stress-related molecules Twist1, Y-box binding protein-1 (YB-1) and androgen receptor (AR) expression in PCa samples treated with or without neoadjuvant ADT were investigated by immunohistochemistry. Intracellular reactive oxygen species and protein expression levels were examined by CM-H2DCFDA and western blot analysis, respectively. Cell proliferation assay and mouse xenograft model were employed to assess tumor growth. RESULTS ADT increased oxidative stress represented by 4-HNE staining in human PCa tissues. In addition, expression of Twist1 and YB-1 was upregulated by ADT, resulting in AR overexpression (Fig. A and Table). In LNCaP and 22Rv1 cells, androgen deprivation increased intracellular reactive oxygen species and evoked Twist1, YB-1, and AR overexpression, resulting in cell growth in a castration-resistant manner. This growth was alleviated by an electrophile supporting glutathione production, N-acetyl-cysteine (NAC). NAC also decreased LNCaP and 22Rv1 tumor growth in castrated and noncastrated mice (Fig. B). CONCLUSIONS ADT induced oxidative stress in in vitro and in human PCa. Antioxidant therapy using NAC appears a promising therapeutic modality for PCa. © 2012 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 187Issue 4SApril 2012Page: e318-e319 Peer Review Report Advertisement Copyright & Permissions© 2012 by American Urological Association Education and Research, Inc.MetricsAuthor Information Masaki Shiota Fukuoka, Japan More articles by this author YooHyun Song Fukuoka, Japan More articles by this author Ario Takeuchi Fukuoka, Japan More articles by this author Akira Yokomizo Fukuoka, Japan More articles by this author Eiji Kashiwagi Fukuoka, Japan More articles by this author Kentaro Kuroiwa Fukuoka, Japan More articles by this author Katsunori Tatsugami Fukuoka, Japan More articles by this author Takeshi Uchiumi Fukuoka, Japan More articles by this author Yoshinao Oda Fukuoka, Japan More articles by this author Seiji Naito Fukuoka, Japan More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...