This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend 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 Rao, A. Articles by Cramer, S. D. Search for Related Content PubMed PubMed Citation Articles by Rao, A. Articles by Cramer, S. D.

Vitamin D Receptor and p21/WAF1 Are Targets of Genistein and 1,25-Dihydroxyvitamin D₃ in Human Prostate Cancer Cells

Departments of ¹ Cancer Biology and ² Radiation Oncology, Wake Forest University School of Medicine, Winston-Salem, North Carolina, and ³ Department of Biological Sciences, University of Notre Dame, Notre Dame, Indiana

We investigated mechanisms by which genistein and 1,25-dihydroxyvitamin D₃ [1,25(OH)₂D₃] act synergistically to inhibit the growth of the human prostate cancer cell line LNCaP. We demonstrate that 1,25(OH)₂D₃ and genistein cooperate to up-regulate the vitamin D receptor protein by increasing the stability of the vitamin D receptor. Genistein and 1,25(OH)₂D₃ also cooperate to up-regulate the levels of p21/WAF1 (p21). Small interfering RNA-mediated knockdown of p21 expression showed that p21 is essential for significant growth inhibition of LNCaP cells in response to either compound or their combination. We conclude that one mechanism of synergism between genistein and 1,25(OH)₂D₃ is through genistein modulation of vitamin D signaling.

This article has been cited by other articles:

				D. Su, S. Zhu, X. Han, Y. Feng, H. Huang, G. Ren, L. Pan, Y. Zhang, J. Lu, and B. Huang BMP4-Smad Signaling Pathway Mediates Adriamycin-induced Premature Senescence in Lung Cancer Cells J. Biol. Chem., May 1, 2009; 284(18): 12153 - 12164. [Abstract] [Full Text] [PDF]

				Y. Yin, J. Ni, M. Chen, Y. Guo, and S. Yeh RRR-{alpha}-Vitamin E Succinate Potentiates the Antitumor Effect of Calcitriol in Prostate Cancer without Overt Side Effects Clin. Cancer Res., January 1, 2009; 15(1): 190 - 200. [Abstract] [Full Text] [PDF]

				S. Majid, N. Kikuno, J. Nelles, E. Noonan, Y. Tanaka, K. Kawamoto, H. Hirata, L. C. Li, H. Zhao, S. T. Okino, et al. Genistein Induces the p21WAF1/CIP1 and p16INK4a Tumor Suppressor Genes in Prostate Cancer Cells by Epigenetic Mechanisms Involving Active Chromatin Modification Cancer Res., April 15, 2008; 68(8): 2736 - 2744. [Abstract] [Full Text] [PDF]

				S. Swami, A. V. Krishnan, J. Moreno, R. B. Bhattacharyya, D. M. Peehl, and D. Feldman Calcitriol and Genistein Actions to Inhibit the Prostaglandin Pathway: Potential Combination Therapy to Treat Prostate Cancer J. Nutr., January 1, 2007; 137(1): 205S - 210S. [Abstract] [Full Text] [PDF]

				A. Misawa, J. Inoue, Y. Sugino, H. Hosoi, T. Sugimoto, F. Hosoda, M. Ohki, I. Imoto, and J. Inazawa Methylation-Associated Silencing of the Nuclear Receptor 1I2 Gene in Advanced-Type Neuroblastomas, Identified by Bacterial Artificial Chromosome Array-Based Methylated CpG Island Amplification Cancer Res., November 15, 2005; 65(22): 10233 - 10242. [Abstract] [Full Text] [PDF]

				A. P. B. Dackiw, S. Ezzat, P. Huang, W. Liu, and S. L. Asa Vitamin D3 Administration Induces Nuclear p27 Accumulation, Restores Differentiation, and Reduces Tumor Burden in a Mouse Model of Metastatic Follicular Thyroid Cancer Endocrinology, December 1, 2004; 145(12): 5840 - 5846. [Abstract] [Full Text] [PDF]