title: Berberine suppresses androgen receptor signaling in prostate cancer.
abstract: The androgen receptor (AR) is critical in the normal development and function of the prostate, as well as in prostate carcinogenesis. Androgen deprivation therapy is the mainstay in the treatment of advanced prostate cancer; however, after an initial response, the disease inevitably progresses to castration-resistant prostate cancer (CRPC). Recent evidence suggests that continued AR activation, sometimes in a ligand-independent manner, is commonly associated with the development of CRPC. Thus, novel agents targeting the AR are urgently needed as a strategic step in developing new therapies for this disease state. In this study, we investigated the effect of berberine on AR signaling in prostate cancer. We report that berberine decreased the transcriptional activity of AR. Berberine did not affect AR mRNA expression, but induced AR protein degradation. Several ligand-binding, domain-truncated AR splice variants have been identified, and these variants are believed to promote the development of CRPC in patients. Interestingly, we found that these variants were more susceptible to berberine-induced degradation than the full-length AR. Furthermore, although the growth of LNCaP xenografts in nude mice was inhibited by berberine, and AR expression was reduced in the tumors, the morphology and AR expression in normal prostates were not affected. This study is the first to show that berberine suppresses AR signaling and suggests that berberine, or its derivatives, presents a promising agent for the prevention and/or treatment of prostate cancer.
authors: Department of Pathology and Laboratory Medicine, Tulane University School of Medicine, New Orleans, LA 70112, USA.
authors: Jing
authors: J
authors: Li
authors: Bo
authors: B
authors: Cao
authors: Xichun
authors: X
authors: Liu
authors: Xueqi
authors: X
authors: Fu
authors: Zhenggang
authors: Z
authors: Xiong
authors: Li
authors: L
authors: Chen
authors: Oliver
authors: O
authors: Sartor
authors: Yan
authors: Y
authors: Dong
authors: Haitao
authors: H
authors: Zhang
references: Mol Endocrinol. 2009 Dec;23(12):1963-72
references: 19855091
references: Biochem Biophys Res Commun. 2000 Sep 16;276(1):144-50
references: 11006097
references: Cancer Res. 2008 Jun 1;68(11):4447-54
references: 18519708
references: Prostate. 2010 Mar 1;70(4):390-400
references: 19866465
references: Cancer Res. 2001 May 1;61(9):3550-5
references: 11325816
references: Essays Biochem. 2004;40:41-58
references: 15242338
references: J Biol Chem. 2005 Jul 22;280(29):26729-34
references: 15937340
references: Biochem Biophys Res Commun. 2009 Jan 9;378(2):174-8
references: 19000652
references: Cancer Res. 2006 Mar 1;66(5):2815-25
references: 16510604
references: N Engl J Med. 1995 May 25;332(21):1393-8
references: 7723794
references: Int J Oncol. 2009 May;34(5):1221-30
references: 19360335
references: Lab Invest. 2008 Oct;88(10):1049-56
references: 18762779
references: Cancer Res. 2009 Jan 1;69(1):16-22
references: 19117982
references: Nat Med. 1997 Apr;3(4):402-8
references: 9095173
references: Prostate. 2007 Apr 1;67(5):509-20
references: 17221841
references: Nat Med. 2000 Jun;6(6):703-6
references: 10835690
references: Cell Cycle. 2009 Dec 15;8(24):4155-67
references: 19946220
references: Mol Cell. 2005 May 27;18(5):601-7
references: 15916966
references: Cancer Res. 2006 Nov 15;66(22):11047-54
references: 17108144
references: Cancer Res. 2009 Oct 15;69(20):8141-9
references: 19808968
references: Cancer Res. 2002 Nov 15;62(22):6606-14
references: 12438256
references: Cancer Res. 2009 Mar 15;69(6):2305-13
references: 19244107
references: Clin Cancer Res. 2002 May;8(5):986-93
references: 12006510
references: Biomed Chromatogr. 1999 Nov;13(7):442-4
references: 10534753
references: Mutat Res. 2009 Mar 9;662(1-2):75-83
references: 19159633
references: Mol Cell Endocrinol. 2008 Nov 25;295(1-2):115-20
references: 18782595
references: Cancer Res. 2008 Aug 1;68(15):6407-15
references: 18676866
references: Toxicol Appl Pharmacol. 2008 May 15;229(1):33-43
references: 18275980
references: Mol Endocrinol. 2004 Oct;18(10):2409-23
references: 15205473
references: Nat Med. 2004 Jan;10(1):33-9
references: 14702632
references: Oncogene. 2008 Jun 26;27(28):3986-98
references: 18332867
references: J Clin Oncol. 2010 Mar 20;28(9):1496-501
references: 20159814
references: J Biol Chem. 1996 Nov 8;271(45):28697-702
references: 8910505
references: Cancer Cell. 2006 Oct;10(4):309-19
references: 17045208
references: Cancer Cell. 2010 Jun 15;17(6):535-46
references: 20541699
references: CA Cancer J Clin. 2010 Sep-Oct;60(5):277-300
references: 20610543
references: Arch Toxicol. 2007 Oct;81(10):719-28
references: 17673978
references: J Clin Oncol. 2010 Mar 20;28(9):1489-95
references: 20159823
references: Mol Pharmacol. 2010 Nov;78(5):846-54
references: 20709811
references: Am J Pathol. 2004 Jan;164(1):217-27
references: 14695335
references: Mol Cancer Ther. 2005 Jul;4(7):1047-55
references: 16020662
references: Cancer Res. 2008 Jul 1;68(13):5469-77
references: 18593950
references: Mol Cancer Ther. 2006 Feb;5(2):296-308
references: 16505103
references: J Clin Invest. 2010 Aug;120(8):2715-30
references: 20644256
references: Food Chem Toxicol. 2010 Apr;48(4):1105-10
references: 20138204
references: Clin Cancer Res. 2011 Jun 1;17(11):3520-6
references: 21471425
references: Mol Cancer Ther. 2008 Oct;7(10):3195-202
references: 18852123
references: Cancer Res. 1999 Jun 1;59(11):2511-5
references: 10363963
references: Cell Stress Chaperones. 2002 Jan;7(1):55-64
references: 11894840