Equol inhibits prostate cancer growth through degradation of androgen receptor by S-phase kinase-associated protein 2

Momoe Itsumi, Masaki Shiota, Ario Takeuchi, Eiji Kashiwagi, Junichi Inokuchi, Katsunori Tatsugami, Shunichi Kajioka, Takeshi Uchiumi, Seiji Naito, Masatoshi Eto, Akira Yokomizo

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

Chemopreventive and potential therapeutic effects of soy isoflavones have been shown to be effective in numerous preclinical studies as well as clinical studies in prostate cancer. Although the inhibition of androgen receptor signaling has been supposed as one mechanism underlying their effects, the precise mechanism of androgen receptor inhibition remains unclear. Thus, this study aimed to clarify their mechanism. Among soy isoflavones, equol suppressed androgen receptor as well as prostate-specific antigen expression most potently in androgen-dependent LNCaP cells. However, the inhibitory effect on androgen receptor expression and activity was less prominent in castration-resistant CxR and 22Rv1 cells. Consistently, cell proliferation was suppressed and cellular apoptosis was induced by equol in LNCaP cells, but less so in CxR and 22Rv1 cells. We revealed that the proteasome pathway through S-phase kinase-associated protein 2 (Skp2) was responsible for androgen receptor suppression. Taken together, soy isoflavones, especially equol, appear to be promising as chemopreventive and therapeutic agents for prostate cancer based on the fact that equol augments Skp2-mediated androgen receptor degradation. Moreover, because Skp2 expression was indicated to be crucial for the effect of soy isoflavones, soy isoflavones may be applicable for precancerous and cancerous prostates.

Original languageEnglish
Pages (from-to)1022-1028
Number of pages7
JournalCancer Science
Volume107
Issue number7
DOIs
Publication statusPublished - Jul 1 2016

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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