Trilostane, an inhibitor of 3β-hydroxysteroid dehydrogenase, has an agonistic activity on androgen receptor in human prostate cancer cells

Cancer Lett. 2010 Nov 28;297(2):226-30. doi: 10.1016/j.canlet.2010.05.015. Epub 2010 Jun 17.

Abstract

The intracellular androgen metabolism and cell activity in prostate cancer cells with mutated (LNCaP-FGC) or wild-type (VCaP) androgen receptors in the presence of trilostane, an inhibitor of 3β-hydroxysteroid dehydrogenase, were examined. Trilostane suppressed the intracellular production of androstenedione, testosterone, and dihydrotestosterone from dehydroepiandrosterone in LNCaP-FGC cells. In both LNCaP-FGC and VCaP cell types, the prostate-specific antigen (PSA) levels in media were increased by trilostane alone in a concentration-dependent manner. Both cells pretreated with trilostane showed a dose-dependent decrease in PSA production with bicalutamide (P<0.001). Trilostane should be used with particular concern when treating prostate cancer.

MeSH terms

  • 3-Hydroxysteroid Dehydrogenases / antagonists & inhibitors*
  • Androgens* / biosynthesis
  • Cell Line, Tumor
  • Chromatography, Liquid
  • Dehydroepiandrosterone / metabolism
  • Dihydrotestosterone / analogs & derivatives*
  • Dihydrotestosterone / pharmacology
  • Enzyme Inhibitors / pharmacology
  • Humans
  • Male
  • Mass Spectrometry
  • Prostatic Neoplasms / drug therapy*
  • Prostatic Neoplasms / metabolism*
  • Prostatic Neoplasms / pathology
  • Receptors, Androgen / metabolism
  • Testosterone / metabolism

Substances

  • Androgens
  • Enzyme Inhibitors
  • Receptors, Androgen
  • Dihydrotestosterone
  • Testosterone
  • Dehydroepiandrosterone
  • 3-Hydroxysteroid Dehydrogenases
  • trilostane