Kartogenin Inhibits Prostate Cancer Cell Growth Through Smad2 Activation and Decreases Androgen Receptor Nuclear Localization

Anticancer Res. 2021 Oct;41(10):4753-4759. doi: 10.21873/anticanres.15290.

Abstract

Background/aim: De-differentiation is a key step for the progression of cancer cells. This study investigated the anti-tumor effect of kartogenin (KGN), which has the ability to differentiate cells, on prostate cancer (PC) cells.

Materials and methods: The effects of KGN on androgen receptor (AR) nuclear localization, prostate-specific antigen (PSA) expression, and Smad2 activation as well as the growth of PC cell lines (LNCaP, 22Rv1 and PC-3) were analyzed.

Results: KGN significantly inhibited growth of AR-expressing LNCaP and 22Rv1 cells but not of AR-lacking PC-3 cells. KGN decreased AR nuclear localization and PSA expression, but did not enhance the anti-tumor effect of bicalutamide in LNCaP cells. KGN activated Smad2 both in the absence and presence of TGF-β1. KGN also inhibited growth of docetaxel-resistant PC cells, 22Rv1DR, and re-sensitized them to the agent.

Conclusion: KGN has a potential as a novel therapeutic for PC patients after treatment failure.

Keywords: Prostate cancer; Smad2; androgen receptor; kartogenin.

MeSH terms

  • Anilides / pharmacology*
  • Antineoplastic Agents / pharmacology*
  • Cell Line, Tumor
  • Cell Nucleus / metabolism*
  • Cell Proliferation / drug effects
  • Drug Resistance, Neoplasm / drug effects
  • Humans
  • Male
  • Phosphorylation / drug effects
  • Phthalic Acids / pharmacology*
  • Prostate-Specific Antigen / metabolism
  • Prostatic Neoplasms / pathology
  • Receptors, Androgen / metabolism*
  • Smad2 Protein / metabolism*
  • Transforming Growth Factor beta1 / pharmacology

Substances

  • AR protein, human
  • Anilides
  • Antineoplastic Agents
  • Phthalic Acids
  • Receptors, Androgen
  • SMAD2 protein, human
  • Smad2 Protein
  • Transforming Growth Factor beta1
  • Prostate-Specific Antigen
  • kartogenin