Genistein induces the p21WAF1/CIP1 and p16INK4a tumor suppressor genes in prostate cancer cells by epigenetic mechanisms involving active chromatin modification. Export

@article{citeulike:3125161, abstract = {Genistein (4',5,7-trihydroxyisoflavone) is the most abundant isoflavone found in the soybean. The effects of genistein on various cancer cell lines have been extensively studied but the precise molecular mechanisms are not known. We report here the epigenetic mechanism of the action of genistein on androgen-sensitive (LNCaP) and androgen-insensitive (DuPro) human prostate cancer cell lines. Genistein induced the expression of tumor suppressor genes p21 (WAF1/CIP1/KIP1) and p16 (INK4a) with a concomitant decrease in cyclins. There was a G(0)-G(1) cell cycle arrest in LNCaP cells and a G(2)-M arrest in DuPro cells after genistein treatment. Genistein also induced apoptosis in DuPro cells. DNA methylation analysis revealed the absence of p21 promoter methylation in both cell lines. The effect of genistein on chromatin remodeling has not been previously reported. We found that genistein increased acetylated histones 3, 4, and H3/K4 at the p21 and p16 transcription start sites. Furthermore, we found that genistein treatment also increased the expression of histone acetyl transferases that function in transcriptional activation. This is the first report on epigenetic regulation of various genes by genistein through chromatin remodeling in prostate cancer. Altogether, our data provide new insights into the epigenetic mechanism of the action of genistein that may contribute to the chemopreventive activity of this dietary isoflavone and have important implications for epigenetic therapy.}, address = {Department of Urology, Veterans Affairs Medical Center, University of California, San Francisco, California 94121, USA.}, author = {Majid, S. and Kikuno, N. and Nelles, J. and Noonan, E. and Tanaka, Y. and Kawamoto, K. and Hirata, H. and Li, L. C. and Zhao, H. and Okino, S. T. and Place, R. F. and Pookot, D. and Dahiya, R.}, citeulike-article-id = {3125161}, citeulike-linkout-0 = {http://dx.doi.org/10.1158/0008-5472.CAN-07-2290}, citeulike-linkout-1 = {http://view.ncbi.nlm.nih.gov/pubmed/18413741}, citeulike-linkout-2 = {http://www.hubmed.org/display.cgi?uids=18413741}, day = {15}, doi = {10.1158/0008-5472.CAN-07-2290}, issn = {1538-7445}, journal = {Cancer research}, keywords = {epigenetic, genistein}, month = {April}, number = {8}, pages = {2736--2744}, posted-at = {2008-08-16 02:30:23}, priority = {2}, title = {Genistein induces the p21WAF1/CIP1 and p16INK4a tumor suppressor genes in prostate cancer cells by epigenetic mechanisms involving active chromatin modification.}, url = {http://dx.doi.org/10.1158/0008-5472.CAN-07-2290}, volume = {68}, year = {2008} }

TY - JOUR ID - citeulike:3125161 L3 - citeulike-article-id:3125161 N2 - Genistein (4',5,7-trihydroxyisoflavone) is the most abundant isoflavone found in the soybean. The effects of genistein on various cancer cell lines have been extensively studied but the precise molecular mechanisms are not known. We report here the epigenetic mechanism of the action of genistein on androgen-sensitive (LNCaP) and androgen-insensitive (DuPro) human prostate cancer cell lines. Genistein induced the expression of tumor suppressor genes p21 (WAF1/CIP1/KIP1) and p16 (INK4a) with a concomitant decrease in cyclins. There was a G(0)-G(1) cell cycle arrest in LNCaP cells and a G(2)-M arrest in DuPro cells after genistein treatment. Genistein also induced apoptosis in DuPro cells. DNA methylation analysis revealed the absence of p21 promoter methylation in both cell lines. The effect of genistein on chromatin remodeling has not been previously reported. We found that genistein increased acetylated histones 3, 4, and H3/K4 at the p21 and p16 transcription start sites. Furthermore, we found that genistein treatment also increased the expression of histone acetyl transferases that function in transcriptional activation. This is the first report on epigenetic regulation of various genes by genistein through chromatin remodeling in prostate cancer. Altogether, our data provide new insights into the epigenetic mechanism of the action of genistein that may contribute to the chemopreventive activity of this dietary isoflavone and have important implications for epigenetic therapy. IS - 8 JF - Cancer research SN - 1538-7445 AD - Department of Urology, Veterans Affairs Medical Center, University of California, San Francisco, California 94121, USA. EP - 2744 TI - Genistein induces the p21WAF1/CIP1 and p16INK4a tumor suppressor genes in prostate cancer cells by epigenetic mechanisms involving active chromatin modification. VL - 68 SP - 2736 KW - epigenetic KW - genistein AU - Majid, S AU - Kikuno, N AU - Nelles, J AU - Noonan, E AU - Tanaka, Y AU - Kawamoto, K AU - Hirata, H AU - Li, LC AU - Zhao, H AU - Okino, ST AU - Place, RF AU - Pookot, D AU - Dahiya, R PY - 2008/04/15/ UR - http://dx.doi.org/10.1158/0008-5472.CAN-07-2290 ER -