A novel dietary flavonoid fisetin inhibits androgen receptor signaling and tumor growth in athymic nude mice.

作者: Naghma Khan , Mohammad Asim , Farrukh Afaq , Mohammad Abu Zaid , Hasan Mukhtar

DOI: 10.1158/0008-5472.CAN-08-0240

关键词:

摘要: Androgen receptor (AR)-mediated signaling plays an important role in the development and progression of prostate cancer (PCa). Hormonal therapies, mainly with combinations antiandrogens androgen deprivation, are mainstay treatment for advanced disease. However, emergence resistance largely due to inefficient antihormone action limits their therapeutic usefulness. Here, we report that fisetin, a novel dietary flavonoid, acts as AR ligand by competing high-affinity interact binding domain AR. We show this physical interaction results substantial decrease stability amino-terminal/carboxyl-terminal (N-C) This blunting AR-mediated transactivation target genes including prostate-specific antigen (PSA). In addition, LNCaP cells fisetin decreased protein levels, part, decreasing its promoter activity accelerating degradation. Fisetin also synergized Casodex inducing apoptosis cells. Treatment athymic nude mice implanted AR-positive CWR22Rupsilon1 human PCa resulted inhibition tumor growth reduction serum PSA levels. These data identify inhibitor axis suggest it could be useful chemopreventive chemotherapeutic agent delay PCa.

参考文章(26)
Grant Buchanan, Ryan A. Irvine, Gerhard A. Coetzee, Wayne D. Tilley, Contribution of the androgen receptor to prostate cancer predisposition and progression. Cancer and Metastasis Reviews. ,vol. 20, pp. 207- 223 ,(2001) , 10.1023/A:1015531326689
Xianghua Lu, Jae in Jung, Han Jin Cho, Do Young Lim, Hyun Sook Lee, Hyang Sook Chun, Dae Young Kwon, Jung Han Park, Fisetin Inhibits the Activities of Cyclin-Dependent Kinases Leading to Cell Cycle Arrest in HT-29 Human Colon Cancer Cells Journal of Nutrition. ,vol. 135, pp. 2884- 2890 ,(2005) , 10.1093/JN/135.12.2884
A. Jemal, R. Siegel, E. Ward, T. Murray, J. Xu, M. J. Thun, Cancer statistics, 2007. CA: A Cancer Journal for Clinicians. ,vol. 57, pp. 43- 66 ,(2007) , 10.3322/CANJCLIN.57.1.43
A Q Haddad, V Venkateswaran, L Viswanathan, S J Teahan, N E Fleshner, L H Klotz, Novel antiproliferative flavonoids induce cell cycle arrest in human prostate cancer cell lines. Prostate Cancer and Prostatic Diseases. ,vol. 9, pp. 68- 76 ,(2006) , 10.1038/SJ.PCAN.4500845
Petra Hååg, Jasmin Bektic, Georg Bartsch, Helmut Klocker, Iris E. Eder, Androgen receptor down regulation by small interference RNA induces cell growth inhibition in androgen sensitive as well as in androgen independent prostate cancer cells. The Journal of Steroid Biochemistry and Molecular Biology. ,vol. 96, pp. 251- 258 ,(2005) , 10.1016/J.JSBMB.2005.04.029
Charlie D Chen, Derek S Welsbie, Chris Tran, Sung Hee Baek, Randy Chen, Robert Vessella, Michael G Rosenfeld, Charles L Sawyers, Molecular determinants of resistance to antiandrogen therapy Nature Medicine. ,vol. 10, pp. 33- 39 ,(2004) , 10.1038/NM972
Vaqar Mustafa Adhami, Hasan Mukhtar, Anti-oxidants from green tea and pomegranate for chemoprevention of prostate cancer. Molecular Biotechnology. ,vol. 37, pp. 52- 57 ,(2007) , 10.1007/S12033-007-0047-8
Daisuke Ichimatsu, Masaaki Nomura, Seiji Nakamura, Shuzo Moritani, Koichi Yokogawa, Shinjiro Kobayashi, Tatsuo Nishioka, Ken-ichi Miyamoto, Structure-activity relationship of flavonoids for inhibition of epidermal growth factor-induced transformation of JB6 Cl 41 cells Molecular Carcinogenesis. ,vol. 46, pp. 436- 445 ,(2007) , 10.1002/MC.20292
Yen-Chou Chen, Shing-Chuan Shen, Woan-Rouh Lee, Hui-Yi Lin, Ching-Huai Ko, Chun-Ming Shih, Ling-Ling Yang, Wogonin and fisetin induction of apoptosis through activation of caspase 3 cascade and alternative expression of p21 protein in hepatocellular carcinoma cells SK-HEP-1. Archives of Toxicology. ,vol. 76, pp. 351- 359 ,(2002) , 10.1007/S00204-002-0346-6