Genistein inhibits the stemness properties of prostate cancer cells through targeting Hedgehog-Gli1 pathway

Linlin Zhang, Lei Li, Min Jiao, Dapeng Wu, Kaijie Wu, Xiang Li, Guodong Zhu, Lin Yang, Xinyang Wang, Jer Tsong Hsieh, Dalin He

Research output: Contribution to journalArticlepeer-review

70 Scopus citations

Abstract

Cancer stem cells (CSCs) are involved in tumorigenesis and progression of prostate cancer (PCa). Conventional anticancer therapeutics failed to eradicate CSCs, which may eventually lead to the disease relapse and metastasis. Therefore, targeting prostate CSCs may be an ideal strategy to cure PCa. Genistein is a major isoflavone constituent of soybeans and soy products, which has been shown to exhibit potent anticancer effect on many cancers. We have previously reported that genistein can inhibit PCa cell invasion by reversing epithelial to mesenchymal transition, suggesting that genistein may be effective against metastatic PCa. In addition, we have recently demonstrated that PCa tumorsphere cells (TCs) possess CSC properties. Here, we found that tumorsphere formation and colony formation of Pca cells were noticeably suppressed in the presence of genistein. Pretreatment of PCa TCs with genistein also suppressed tumorigenicity in vivo. Additionally, genistein treatment inhibited tumor growth of PCa TCs. Further studies showed that genistein treatment not only led to the down-regulation of PCa CSC markers CD44 in vitro and in vivo, but also inhibited Hedgehog-Gli1 pathway, which may contribute to the anti-CSC effect of genistein in PCa TCs. Therefore, our findings demonstrated that genistein may be a dietary phytochemical with potential to target prostate CSCs.

Original languageEnglish (US)
Pages (from-to)48-57
Number of pages10
JournalCancer Letters
Volume323
Issue number1
DOIs
StatePublished - Oct 1 2012

Keywords

  • Cancer stem cell
  • Genistein
  • Prostate cancer
  • Tumorsphere cell

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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