Docosahexaenoic acid inhibits the growth of hormone-dependent prostate cancer cells by promoting the degradation of the androgen receptor

Mol Med Rep. 2015 Sep;12(3):3769-3774. doi: 10.3892/mmr.2015.3813. Epub 2015 May 21.

Abstract

Epidemiological and preclinical data have demonstrated the preventative effects of ω-3 polyunsaturated fatty acids, including docosahexaenoic acid (DHA), on prostate cancer. However, there are inconsistencies in these previous studies and the underlying mechanisms remain to be elucidated. In the present study, the androgen receptor (AR), which is a transcription factor involved in cell proliferation and prostate carcinogenesis, was identified as a target of DHA. It was revealed that DHA inhibited hormone‑dependent growth of LNCaP prostate cancer cells. Reverse transcription-quantitative polymerase chain reaction analysis revealed that treatment with DHA caused no alteration in the transcribed mRNA expression levels of the AR gene. However, immunoblotting revealed that this treatment reduces the protein expression level of the AR. The androgen‑induced genes were subsequently repressed by treatment with DHA. It was demonstrated that DHA exhibits no effect on the translation process of the AR, however, it promotes the proteasome‑mediated degradation of the AR. Therefore, the present study provided a novel mechanism by which DHA exhibits an inhibitory effect on growth of prostate cancer cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Androgens / genetics
  • Androgens / metabolism
  • Antineoplastic Agents / pharmacology*
  • Cell Line, Tumor
  • Cell Proliferation / drug effects*
  • Docosahexaenoic Acids / pharmacology*
  • Gene Expression Regulation, Neoplastic / drug effects
  • Humans
  • Male
  • Prostate / drug effects
  • Prostate / metabolism
  • Prostate / pathology
  • Prostatic Neoplasms / drug therapy*
  • Prostatic Neoplasms / genetics
  • Prostatic Neoplasms / metabolism
  • Prostatic Neoplasms / pathology
  • Proteolysis / drug effects*
  • Receptors, Androgen / genetics
  • Receptors, Androgen / metabolism*

Substances

  • AR protein, human
  • Androgens
  • Antineoplastic Agents
  • Receptors, Androgen
  • Docosahexaenoic Acids