A FOXC2 inhibitor, MC-1-F2, as a therapeutic candidate for targeting EMT in castration-resistant prostate cancer

Bioorg Med Chem Lett. 2023 Jul 15:91:129369. doi: 10.1016/j.bmcl.2023.129369. Epub 2023 Jun 7.

Abstract

Androgen deprivation therapy (ADT) is the major treatment option for advanced prostate cancer. However, prostate cancer can develop into androgen-independent castration-resistant prostate cancer (CRPC) which is resistant to ADT. An alternative treatment strategy for CRPC can be targeting the epithelial-mesenchymal transition (EMT). EMT is governed by a series of transcription factors of which forkhead box protein C2 (FOXC2) is a central mediator. Our previous research into the inhibition of FOXC2 in breast cancer cells lead to the discovery of MC-1-F2, the first direct inhibitor of FOXC2. In current study on CRPC, MC-1-F2 has shown a decrease in mesenchymal markers, inhibition of cancer stem cell (CSC) properties and decrease in invasive capabilities of CRPC cell lines. We have also demonstrated a synergistic effect between MC-1-F2 and docetaxel treatments, leading to a decrease in docetaxel dosage, suggesting the possible combination therapy of MC-1-F2 and docetaxel for the effective treatment of CRPC.

Keywords: Castration-resistant prostate cancer; Epithelial-mesenchymal transition; Forkhead box protein C2.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Androgen Antagonists
  • Androgens
  • Cell Line, Tumor
  • Docetaxel / pharmacology
  • Epithelial-Mesenchymal Transition
  • Humans
  • Male
  • Prostatic Neoplasms, Castration-Resistant* / drug therapy
  • Prostatic Neoplasms, Castration-Resistant* / metabolism
  • Transcription Factors

Substances

  • Androgen Antagonists
  • Androgens
  • Docetaxel
  • Transcription Factors
  • MC-1-F2