Repression of cell proliferation and androgen receptor activity in prostate cancer cells by 2'-hydroxyflavanone

Anticancer Res. 2013 Oct;33(10):4453-61.

Abstract

Background: Prevention of the development of castration-resistant from hormone-naïve prostate cancer is an important issue in maintaining the quality of life of the patients. We explored the effect of 2'-hydroxyflavanone on proliferation and androgen responsiveness using prostate cancer cell lines.

Materials and methods: To investigate the effect of 2'-hydroxyflavanone on proliferation, prostate cancer cells were treated with 2'-hydroxyflavanone. Androgen-responsiveness in LNCaP cells was confirmed by luciferase assay after transfection of luciferase reporter driven by prostate specific antigen promoter. To detect androgen receptor (AR) expression, reverse transcriptase polymerase chain reaction and western blot analysis were conducted.

Results: 2'-Hydroxyflavanone inhibited the proliferation of PC-3 and DU145 cells by induction of apoptosis. 2'-Hydroxyflavanone inhibited the proliferation of LNCaP cells stimulated by androgens and attenuated androgen-responsiveness through down-regulation of AR protein.

Conclusion: 2'-Hydroxyflavanone not only inhibited proliferation of prostate cancer cells, but also repressed androgen-responsiveness, suggesting that it might be a useful agent in preventing recurrence of prostate cancer.

Keywords: 2’-hydroxyflavanone; Prostate cancer; androgen; androgen receptor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3-Oxo-5-alpha-Steroid 4-Dehydrogenase / metabolism
  • Active Transport, Cell Nucleus / drug effects
  • Androgens / biosynthesis
  • Androstenedione / pharmacology
  • Antineoplastic Agents, Hormonal / pharmacology*
  • Cell Line, Tumor
  • Cell Proliferation / drug effects*
  • Drug Screening Assays, Antitumor
  • Estradiol Dehydrogenases / metabolism
  • Flavanones / pharmacology*
  • Gene Expression
  • Gene Expression Regulation, Neoplastic / drug effects
  • Humans
  • Kallikreins / genetics
  • Kallikreins / metabolism
  • Male
  • Promoter Regions, Genetic
  • Prostate-Specific Antigen / genetics
  • Prostate-Specific Antigen / metabolism
  • Prostatic Neoplasms, Castration-Resistant
  • Receptors, Androgen / genetics
  • Receptors, Androgen / metabolism*

Substances

  • 2'-hydroxyflavanone
  • Androgens
  • Antineoplastic Agents, Hormonal
  • Flavanones
  • Receptors, Androgen
  • Androstenedione
  • Estradiol Dehydrogenases
  • 3-Oxo-5-alpha-Steroid 4-Dehydrogenase
  • KLK3 protein, human
  • Kallikreins
  • Prostate-Specific Antigen