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ROS signaling by NADPH oxidase 5 modulates the proliferation and survival of prostate carcinoma cells.
Mol Carcinog 2016; 55(1):27-39MC

Abstract

Prostate cancer (PCa) is the most commonly diagnosed cancer and second leading cause of male cancer death in Western nations. Thus, new treatment modalities are urgently needed. Elevated production of reactive oxygen species (ROS) by NADPH oxidase (Nox) enzymes is implicated in tumorigenesis of the prostate and other tissues. However, the identity of the Nox enzyme(s) involved in prostate carcinogenesis remains largely unknown. Analysis of radical prostatectomy tissue samples and benign and malignant prostate epithelial cell lines identified Nox5 as an abundantly expressed Nox isoform. Consistently, immunohistochemical staining of a human PCa tissue microarray revealed distinct Nox5 expression in epithelial cells of benign and malignant prostatic glands. shRNA-mediated knockdown of Nox5 impaired proliferation of Nox5-expressing (PC-3, LNCaP) but not Nox5-negative (DU145) PCa cell lines. Similar effects were observed upon ROS ablation via the antioxidant N-acetylcysteine confirming ROS as the mediators. In addition, Nox5 silencing increased apoptosis of PC-3 cells. Concomitantly, protein kinase C zeta (PKCζ) protein levels and c-Jun N-terminal kinase (JNK) phosphorylation were reduced. Moreover, the effect of Nox5 knockdown on PC-3 cell proliferation could be mimicked by pharmacological inhibition of JNK. Collectively, these data indicate that Nox5 is expressed at functionally relevant levels in the human prostate and clinical PCa. Moreover, findings herein suggest that Nox5-derived ROS and subsequent depletion of PKCζ and JNK inactivation play a critical role in modulating intracellular signaling cascades involved in the proliferation and survival of PCa cells. © 2014 The Authors. Molecular Carcinogenesis published by Wiley Periodicals, Inc.

Authors+Show Affiliations

Institute for Biomedical Aging Research, University of Innsbruck, Innsbruck, Austria. Tyrolean Cancer Research Institute, Medical University of Innsbruck, Innsbruck, Austria.Institute for Biomedical Aging Research, University of Innsbruck, Innsbruck, Austria.Department of Urology, Medical University of Innsbruck, Innsbruck, Austria.Institute for Biomedical Aging Research, University of Innsbruck, Innsbruck, Austria.Institute for Biomedical Aging Research, University of Innsbruck, Innsbruck, Austria.Department of Anaesthesiology and Critical Care Medicine, Medical University of Innsbruck, Innsbruck, Austria.Department of Urology, Medical University of Innsbruck, Innsbruck, Austria.Institute for Biomedical Aging Research, University of Innsbruck, Innsbruck, Austria. Tyrolean Cancer Research Institute, Medical University of Innsbruck, Innsbruck, Austria.Department of Urology, Medical University of Innsbruck, Innsbruck, Austria.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

25559363

Citation

Höll, Monika, et al. "ROS Signaling By NADPH Oxidase 5 Modulates the Proliferation and Survival of Prostate Carcinoma Cells." Molecular Carcinogenesis, vol. 55, no. 1, 2016, pp. 27-39.
Höll M, Koziel R, Schäfer G, et al. ROS signaling by NADPH oxidase 5 modulates the proliferation and survival of prostate carcinoma cells. Mol Carcinog. 2016;55(1):27-39.
Höll, M., Koziel, R., Schäfer, G., Pircher, H., Pauck, A., Hermann, M., ... Sampson, N. (2016). ROS signaling by NADPH oxidase 5 modulates the proliferation and survival of prostate carcinoma cells. Molecular Carcinogenesis, 55(1), pp. 27-39. doi:10.1002/mc.22255.
Höll M, et al. ROS Signaling By NADPH Oxidase 5 Modulates the Proliferation and Survival of Prostate Carcinoma Cells. Mol Carcinog. 2016;55(1):27-39. PubMed PMID: 25559363.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - ROS signaling by NADPH oxidase 5 modulates the proliferation and survival of prostate carcinoma cells. AU - Höll,Monika, AU - Koziel,Rafal, AU - Schäfer,Georg, AU - Pircher,Haymo, AU - Pauck,Alexander, AU - Hermann,Martin, AU - Klocker,Helmut, AU - Jansen-Dürr,Pidder, AU - Sampson,Natalie, Y1 - 2015/01/05/ PY - 2014/05/26/received PY - 2014/10/14/revised PY - 2014/11/03/accepted PY - 2015/1/7/entrez PY - 2015/1/7/pubmed PY - 2016/5/25/medline KW - NOX KW - c-Jun N-terminal kinase KW - prostate cancer KW - protein kinase C KW - reactive oxygen species SP - 27 EP - 39 JF - Molecular carcinogenesis JO - Mol. Carcinog. VL - 55 IS - 1 N2 - Prostate cancer (PCa) is the most commonly diagnosed cancer and second leading cause of male cancer death in Western nations. Thus, new treatment modalities are urgently needed. Elevated production of reactive oxygen species (ROS) by NADPH oxidase (Nox) enzymes is implicated in tumorigenesis of the prostate and other tissues. However, the identity of the Nox enzyme(s) involved in prostate carcinogenesis remains largely unknown. Analysis of radical prostatectomy tissue samples and benign and malignant prostate epithelial cell lines identified Nox5 as an abundantly expressed Nox isoform. Consistently, immunohistochemical staining of a human PCa tissue microarray revealed distinct Nox5 expression in epithelial cells of benign and malignant prostatic glands. shRNA-mediated knockdown of Nox5 impaired proliferation of Nox5-expressing (PC-3, LNCaP) but not Nox5-negative (DU145) PCa cell lines. Similar effects were observed upon ROS ablation via the antioxidant N-acetylcysteine confirming ROS as the mediators. In addition, Nox5 silencing increased apoptosis of PC-3 cells. Concomitantly, protein kinase C zeta (PKCζ) protein levels and c-Jun N-terminal kinase (JNK) phosphorylation were reduced. Moreover, the effect of Nox5 knockdown on PC-3 cell proliferation could be mimicked by pharmacological inhibition of JNK. Collectively, these data indicate that Nox5 is expressed at functionally relevant levels in the human prostate and clinical PCa. Moreover, findings herein suggest that Nox5-derived ROS and subsequent depletion of PKCζ and JNK inactivation play a critical role in modulating intracellular signaling cascades involved in the proliferation and survival of PCa cells. © 2014 The Authors. Molecular Carcinogenesis published by Wiley Periodicals, Inc. SN - 1098-2744 UR - https://www.unboundmedicine.com/medline/citation/25559363/ROS_signaling_by_NADPH_oxidase_5_modulates_the_proliferation_and_survival_of_prostate_carcinoma_cells_ L2 - https://doi.org/10.1002/mc.22255 DB - PRIME DP - Unbound Medicine ER -