Andrographolide targets androgen receptor pathway in castration-resistant prostate cancer

Chengfei Liu, Nagalakshmi Nadiminty, Ramakumar Tummala, Jae Yeon Chun, Wei Lou, Yezi Zhu, Meng Sun, Christopher P Evans, Qinghua Zhou, Allen C Gao

Research output: Contribution to journalArticlepeer-review

27 Scopus citations

Abstract

Androgen receptor (AR) signaling not only plays a pivotal role in the development of androgen-dependent prostate cancer but is also important in the growth and survival of castration-resistant prostate cancer (CRPC). The first line of treatment of androgen-dependent prostate cancer is the use of androgen deprivation therapy. However, most patients will eventually relapse due to development of CRPC. Thus, development of a strategy to target AR for treatment of CRPC is urgently needed. The authors have previously identified andrographolide as an inhibitor of interleukin-6, which can suppress tumor growth of prostate cancer cells by screening compounds from the Prestwick Natural compound library. In this study, they identified that andrographolide can inhibit AR expression and prostate cancer cell growth and induce apoptosis. Andrographolide is able to down-regulate AR expression at both mRNA and protein levels, prevents its nuclear translocation, and inhibits transactivation of its target genes. Andrographolide prevents the binding of Hsp90 to AR, resulting in proteasome-mediated AR degradation. Furthermore, andrographolide inhibits castration-resistant C4-2 cell growth by reducing AR expression and activity. Thus, andrographolide can be developed as a potential therapeutic agent for prostate cancer by inhibition of androgen receptor signaling.

Original languageEnglish (US)
Pages (from-to)151-159
Number of pages9
JournalGenes and Cancer
Volume2
Issue number2
DOIs
StatePublished - 2011

Keywords

  • Androgen receptor
  • Andrographolide
  • Prostate cancer

ASJC Scopus subject areas

  • Cancer Research
  • Genetics

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