Capillarisin blocks prostate-specific antigen expression on activation of androgen receptor in prostate carcinoma cells

Ke Hung Tsui, Ying Ling Chang, Tsui Hsia Feng, Chen Pang Hou, Yu Hsiang Lin, Pei Shan Yang, Bing Wei Lee, Horng Heng Juang

研究成果: 雜誌貢獻文章同行評審

9 引文 斯高帕斯(Scopus)

摘要

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.
原文英語
頁(從 - 到)242-249
頁數8
期刊Prostate
78
發行號4
DOIs
出版狀態已發佈 - 3月 2018
對外發佈

ASJC Scopus subject areas

  • 腫瘤科
  • 泌尿科學

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