This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Uzzo, R. G. Articles by Kolenko, V. M. Search for Related Content PubMed PubMed Citation Articles by Uzzo, R. G. Articles by Kolenko, V. M.

Zinc Inhibits Nuclear Factor-B Activation and Sensitizes Prostate Cancer Cells to Cytotoxic Agents

Department of Surgical Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111 [R. G. U.]; Boston Biomedical Research Institute, Watertown, Massachusetts 02472 [P. L., W. H., V. M. K.]; Department of Biochemistry, Boston University School of Medicine, Boston, Massachusetts 02118 [V. L. G.]; Department of Medicine, The University of Chicago, Chicago, Illinois 60637 [N. D.]; Pavlov State Medical University of Saint Petersburg, Saint Petersburg, Russia 197022 [N. Z.]

Prostate carcinogenesis involves transformation of zinc-accumulating normal epithelial cells to malignant cells, which do not accumulate zinc. In this study, we demonstrate by immunoblotting and immunohistochemistry that physiological levels of zinc inhibit activation of nuclear factor (NF)-B transcription factor in PC-3 and DU-145 human prostate cancer cells, reduce expression of NF-B-controlled antiapoptotic protein c-IAP2, and activate c-Jun NH₂-terminal kinases. Preincubation of PC-3 cells with physiological concentrations of zinc sensitized tumor cells to tumor necrosis factor (TNF)-, and paclitaxel mediated cell death as defined by terminal deoxynucleotidyl transferase-mediated nick end labeling assay. These results suggest one possible mechanism for the inhibitory effect of zinc on the development and progression of prostate malignancy and might have important consequences for the prevention and treatment of prostate cancer.

This article has been cited by other articles:

				K. Golovine, P. Makhov, R. G. Uzzo, T. Shaw, D. Kunkle, and V. M. Kolenko Overexpression of the Zinc Uptake Transporter hZIP1 Inhibits Nuclear Factor-{kappa}B and Reduces the Malignant Potential of Prostate Cancer Cells In vitro and In vivo Clin. Cancer Res., September 1, 2008; 14(17): 5376 - 5384. [Abstract] [Full Text] [PDF]

				R. S. M. Shih, S. H. K. Wong, N. W. Schoene, and K. Y. Lei Suppression of Gadd45 Alleviates the G2/M Blockage and the Enhanced Phosphorylation of p53 and p38 in Zinc Supplemented Normal Human Bronchial Epithelial Cells Experimental Biology and Medicine, March 1, 2008; 233(3): 317 - 327. [Abstract] [Full Text] [PDF]

				R. G. Uzzo, P. L. Crispen, K. Golovine, P. Makhov, E. M. Horwitz, and V. M. Kolenko Diverse effects of zinc on NF-{kappa}B and AP-1 transcription factors: implications for prostate cancer progression Carcinogenesis, October 1, 2006; 27(10): 1980 - 1990. [Abstract] [Full Text] [PDF]

				J. Xie and Z. A. Shaikh Cadmium-Induced Apoptosis in Rat Kidney Epithelial Cells Involves Decrease in Nuclear Factor-Kappa B Activity Toxicol. Sci., May 1, 2006; 91(1): 299 - 308. [Abstract] [Full Text] [PDF]

				F. Jin, X. Liu, Z. Zhou, P. Yue, R. Lotan, F. R. Khuri, L. W.K. Chung, and S.-Y. Sun Activation of Nuclear Factor-{kappa}B Contributes to Induction of Death Receptors and Apoptosis by the Synthetic Retinoid CD437 in DU145 Human Prostate Cancer Cells Cancer Res., July 15, 2005; 65(14): 6354 - 6363. [Abstract] [Full Text] [PDF]

				D. Magda, P. Lecane, R. A. Miller, C. Lepp, D. Miles, M. Mesfin, J. E. Biaglow, V. V. Ho, D. Chawannakul, S. Nagpal, et al. Motexafin Gadolinium Disrupts Zinc Metabolism in Human Cancer Cell Lines Cancer Res., May 1, 2005; 65(9): 3837 - 3845. [Abstract] [Full Text] [PDF]

				D. F. Jarrard Does Zinc Supplementation Increase the Risk of Prostate Cancer? Arch Ophthalmol, January 1, 2005; 123(1): 102 - 103. [Full Text] [PDF]

				M. F. McCarty Targeting Multiple Signaling Pathways as a Strategy for Managing Prostate Cancer: Multifocal Signal Modulation Therapy Integr Cancer Ther, December 1, 2004; 3(4): 349 - 380. [Abstract] [PDF]

				P. Schott-Ohly, A. Lgssiar, H.-J. Partke, M. Hassan, N. Friesen, and H. Gleichmann Prevention of Spontaneous and Experimentally Induced Diabetes in Mice With Zinc Sulfate-Enriched Drinking Water Is Associated with Activation and Reduction of NF-{kappa}B and AP-1 in Islets, Respectively Experimental Biology and Medicine, December 1, 2004; 229(11): 1177 - 1185. [Abstract] [Full Text] [PDF]

				S. Mabuchi, M. Ohmichi, Y. Nishio, T. Hayasaka, A. Kimura, T. Ohta, J. Kawagoe, K. Takahashi, N. Yada-Hashimoto, H. Seino-Noda, et al. Inhibition of Inhibitor of Nuclear Factor-{kappa}B Phosphorylation Increases the Efficacy of Paclitaxel in in Vitro and in Vivo Ovarian Cancer Models Clin. Cancer Res., November 15, 2004; 10(22): 7645 - 7654. [Abstract] [Full Text] [PDF]