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• W2157750797 abstract "No AccessJournal of UrologyInvestigative Urology1 Feb 2012Antioxidant 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 Department of Urology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan Equal study contribution. More articles by this author , YooHyun SongYooHyun Song Department of Urology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan Equal study contribution. More articles by this author , Ario TakeuchiArio Takeuchi Department of Urology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan Equal study contribution. More articles by this author , Akira YokomizoAkira Yokomizo Department of Urology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan More articles by this author , Eiji KashiwagiEiji Kashiwagi Department of Urology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan More articles by this author , Kentaro KuroiwaKentaro Kuroiwa Department of Urology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan More articles by this author , Katsunori TatsugamiKatsunori Tatsugami Department of Urology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan More articles by this author , Takeshi UchiumiTakeshi Uchiumi Department of Clinical Chemistry and Laboratory Medicine, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan More articles by this author , Yoshinao OdaYoshinao Oda Department of Anatomic Pathology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan More articles by this author , and Seiji NaitoSeiji Naito Department of Urology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2011.09.147AboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract Purpose: Prostate cancer progression from androgen dependence to castration resistance results at least in part from oxidative stress induced by androgen deprivation therapy. We elucidated the state and the role of oxidative stress induced by androgen deprivation therapy and the possibility of antioxidant therapy in human prostate cancer. Materials and Methods: We investigated 4-HNE (4-hydroxy-2-nonenal histidine adduct) staining, and Twist1, YB-1 and androgen receptor expression by immunohistochemistry in prostate cancer samples treated with or without neoadjuvant androgen deprivation therapy. Intracellular reactive oxygen species and protein expression were examined by CM-H2DCFDA and Western blot analysis, respectively. A cell proliferation assay and a mouse xenograft model were used to assess tumor growth. Results: Androgen deprivation therapy increased oxidative stress, as shown by 4-HNE staining in human prostate cancer tissue. Twist1 and YB-1 expression was up-regulated by androgen deprivation, resulting in androgen receptor over expression. In LNCaP and 22Rv1 cells androgen deprivation increased intracellular reactive oxygen species and evoked Twist1, YB-1 and androgen receptor over expression, resulting in cell growth in a castration resistant manner. Growth was alleviated by N-acetyl-cysteine, an electrophile that supports glutathione production. N-acetyl-cysteine also decreased LNCaP and 22Rv1 tumor growth in castrated and noncastrated mice. Conclusions: Androgen deprivation therapy induced oxidative stress in in vitro and human prostate cancer. Antioxidant therapy using N-acetyl-cysteine appears to be a promising therapeutic modality for prostate cancer. References 1 : Prostate cancer epidemiology. Lancet2003; 361: 859. Google Scholar 2 : Trends and patterns of prostate cancer: what do they suggest?. Epidemiol Rev2001; 23: 3. Google Scholar 3 : The role of androgens and the androgen receptor in prostate cancer. Cancer Lett2002; 187: 1. 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Google Scholar 22 : Role of Nrf2 in the regulation of CD36 and stress protein expression in murine macrophages: activation by oxidatively modified LDL and 4-hydroxynonenal. Circ Res2004; 94: 609. Google Scholar 23 : Mitogenic signaling mediated by oxidants in Ras-transformed fibroblasts. Science1997; 275: 1649. Google Scholar 24 : Inhibition of angiogenesis-driven Kaposi's sarcoma tumor growth in nude mice by oral N-acetylcysteine. Cancer Res2001; 61: 8171. Google Scholar 25 : Transformed and tumor-derived human cells exhibit preferential sensitivity to the thiol antioxidants, N-acetyl cysteine and penicillamine. Cancer Res2002; 62: 1443. Google Scholar 26 : N-acetyl-cysteine enhances growth in BCR-ABL-transformed cells. Cancer Sci2005; 96: 240. Google Scholar 27 : A comparison of lycopene and orchidectomy vs orchidectomy alone in the management of advanced prostate cancer. BJU Int2003; 92: 375. Google Scholar 28 : Is there a benefit from lycopene supplementation in men with prostate cancer?: A systematic review. Prostate Cancer Prostatic Dis2009; 12: 325. Google Scholar 29 : Associations between α-tocopherol, β-carotene, and retinol and prostate cancer survival. Cancer Res2009; 69: 3833. Google Scholar © 2012 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetailsCited byAtala A (2018) Re: Preclinical Efficacy of Growth Hormone-Releasing Hormone Antagonists for Androgen-Dependent and Castration-Resistant Human Prostate CancerJournal of Urology, VOL. 192, NO. 3, (998-999), Online publication date: 1-Sep-2014. Volume 187Issue 2February 2012Page: 707-714 Advertisement Copyright & Permissions© 2012 by American Urological Association Education and Research, Inc.Keywordsprostateacetylcysteineprostatic neoplasmsdisease progressionandrogen antagonistsAcknowledgmentsNoriko Hakoda and Seiko Kamori provided technical assistance.MetricsAuthor Information Masaki Shiota Department of Urology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan Equal study contribution. More articles by this author YooHyun Song Department of Urology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan Equal study contribution. More articles by this author Ario Takeuchi Department of Urology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan Equal study contribution. More articles by this author Akira Yokomizo Department of Urology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan More articles by this author Eiji Kashiwagi Department of Urology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan More articles by this author Kentaro Kuroiwa Department of Urology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan More articles by this author Katsunori Tatsugami Department of Urology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan More articles by this author Takeshi Uchiumi Department of Clinical Chemistry and Laboratory Medicine, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan More articles by this author Yoshinao Oda Department of Anatomic Pathology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan More articles by this author Seiji Naito Department of Urology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan More articles by this author Expand All Advertisement PDF downloadLoading ..." @default.
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• W2157750797 title "Antioxidant Therapy Alleviates Oxidative Stress by Androgen Deprivation and Prevents Conversion From Androgen Dependent to Castration Resistant Prostate Cancer" @default.
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