Omega-3 fatty acid inhibition of prostate cancer progression to hormone independence is associated with suppression of mTOR signaling and androgen receptor expression

Nutr Cancer. 2011;63(5):771-7. doi: 10.1080/01635581.2011.570892. Epub 2011 Jun 11.

Abstract

Currently, progression of prostate cancer to androgen independence remains the primary obstacle to improved survival. In order to improve overall survival, novel treatment strategies that are based upon specific molecular mechanisms that prolong the androgen-dependent state and that are useful for androgen-independent disease need to be identified. Both epidemiological as well as preclinical data suggest that omega-3 fatty acids are effective primary tumor prevention agents; however, their efficacy at preventing and treating refractory prostate cancer has not been as thoroughly investigated. We used an in vitro model of androgen ablation to determine the effect of treatment with omega-3 fatty acids on the progression to an androgen-independent state. The omega-3 fatty acids docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) were able to prevent progression of LNCaP cells while the omega-6 fatty acid arachidonic acid (AA) actually promoted cell growth under conditions of hormone depletion. These results correlated with a decrease in the expression of the androgen receptor as well as suppression of the Akt/mTOR signaling pathway. Connecting the mechanisms by which omega-3 fatty acids affect phenotypic outcome is important for effective exploitation of these nutrient agents as a therapeutic approach. Understanding these processes is critical for the development of effective dietary intervention strategies that improve overall survival.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Androgens / metabolism*
  • Cell Line, Tumor
  • Cell Proliferation
  • Clone Cells
  • Docosahexaenoic Acids / metabolism
  • Eicosapentaenoic Acid / metabolism
  • Fatty Acids, Omega-3 / metabolism*
  • Humans
  • Male
  • Neoplasm Proteins / metabolism*
  • Phosphorylation
  • Prostatic Neoplasms / diet therapy
  • Prostatic Neoplasms / metabolism*
  • Protein Processing, Post-Translational
  • Proto-Oncogene Proteins c-akt / metabolism
  • Receptors, Androgen / metabolism*
  • Signal Transduction*
  • TOR Serine-Threonine Kinases / metabolism*

Substances

  • AR protein, human
  • Androgens
  • Fatty Acids, Omega-3
  • Neoplasm Proteins
  • Receptors, Androgen
  • Docosahexaenoic Acids
  • Eicosapentaenoic Acid
  • MTOR protein, human
  • TOR Serine-Threonine Kinases
  • Proto-Oncogene Proteins c-akt