Capillarisin blocks prostate‐specific antigen expression on activation of androgen receptor in prostate carcinoma cells. Issue 4 (22nd November 2017)

• Record Type: Journal Article
• Authors: Tsui, Ke‐Hung; Chang, Ying‐Ling; Feng, Tsui‐Hsia; Hou, Chen‐Pang; Lin, Yu‐Hsiang; Yang, Pei‐Shan; Lee, Bing‐Wei; Juang, Horng‐Heng
• Is Part Of: Prostate. Volume 78:Issue 4(2018)
• Page Start: 242
• Page End: 249
• Publication Date: 2017-11-22
• Subjects: androgen receptor -- capillarisin -- prostate -- prostate specific antigen; Prostate -- Diseases -- Periodicals; 616
• DOI: 10.1002/pros.23463
• Languages: English
• ISSNs: 0270-4137

Abstract

Abstract : Background: Capillarisin (Cap), an active ingredient of Artemisia capillaris extracts, has known for its anti‐inflammatory, antioxidant, and anticancer properties. Functions of Cap in prostate cancer are not clear. We investigate effects of Cap on downregulation of prostate specific antigen (PSA) via modulation of androgen receptor (AR) in prostate carcinoma cells. Methods: Cell proliferation was measured by water‐soluble tetrazolium‐1 (WST‐1) cell proliferation assays. The PSA and AR expressions were assessed by immunoblotting and RT‐qPCR assays. Effects of Cap on PSA expressions were determined by ELISA, immunoblotting, and reporter assays. Co‐immunoprecipitation and immunoblotting assays were used to define the effects of Cap on dissociation of AR‐heat shock protein 90 (Hsp90) interaction. Results: Cap inhibited LNCaP cell growth in a dose‐ and/or time‐dependent way without inducing poly ADP‐Ribose Polymerase (PARP) cleavage. Cap not only effectively suppressed AR and PSA protein expressions, but also attenuated activations of synthetic androgen (R1881) on PSA promoter activity dose‐ and time‐dependently. The Cap pretreatment abrogated effects of R1881 on AR activity by reducing AR translocation to the nucleus. Immunoblotting assays indicated that Cap promoted a degradation of AR proteins dose‐dependently in either cycloheximide pretreated‐LNCaP cells or AR‐ectopic expressed PC‐3 cells. Pretreatment of MG132, a proteasome inhibitor, attenuated effect of Cap on AR degradation. Cap lessened AR stability by dissociation of AR‐Hsp90 interaction. Conclusions: Our results indicated that Cap inhibited growth of LNCaP cells. Cap effectively suppressed androgen activation on AR‐mediated transactivation, which is AR‐dependent through AR degradation and dissociation of AR‐Hsp90 in prostate carcinoma cells.