Faculty Collaboration Database

Effect of dietary polyunsaturated fatty acids on castration-resistant Pten-null prostate cancer. Carcinogenesis 2012 Feb;33(2):404-12

Date

12/14/2011

Pubmed ID

22159221

Pubmed Central ID

PMC3271270

DOI

10.1093/carcin/bgr290

Scopus ID

2-s2.0-84863047452 (requires institutional sign-in at Scopus site)   44 Citations

Abstract

A common treatment of advanced prostate cancer involves the deprivation of androgens. Despite the initial response to hormonal therapy, eventually all the patients relapse. In the present study, we sought to determine whether dietary polyunsaturated fatty acid (PUFA) affects the development of castration-resistant prostate cancer. Cell culture, patient tissue microarray, allograft, xenograft, prostate-specific Pten knockout and omega-3 desaturase transgenic mouse models in conjunction with dietary manipulation, gene knockdown and knockout approaches were used to determine the effect of dietary PUFA on castration-resistant Pten-null prostate cancer. We found that deletion of Pten increased androgen receptor (AR) expression and Pten-null prostate cells were castration resistant. Omega-3 PUFA slowed down the growth of castration-resistant tumors as compared with omega-6 PUFA. Omega-3 PUFA decreased AR protein to a similar extent in tumor cell cytosolic and nuclear fractions but had no effect on AR messenger RNA level. Omega-3 PUFA treatment appeared to accelerate AR protein degradation, which could be blocked by proteasome inhibitor MG132. Knockdown of AR significantly slowed down prostate cancer cell proliferation in the absence of androgens. Our data suggest that omega-3 PUFA inhibits castration-resistant prostate cancer in part by accelerating proteasome-dependent degradation of the AR protein. Dietary omega-3 PUFA supplementation in conjunction with androgen ablation may significantly delay the development of castration-resistant prostate cancer in patients compared with androgen ablation alone.

Author List

Wang S, Wu J, Suburu J, Gu Z, Cai J, Axanova LS, Cramer SD, Thomas MJ, Perry DL, Edwards IJ, Mucci LA, Sinnott JA, Loda MF, Sui G, Berquin IM, Chen YQ

Author

Michael J. Thomas PhD Professor in the Pharmacology and Toxicology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Animals
Cell Line, Tumor
Cell Proliferation
Cells, Cultured
Dietary Fats, Unsaturated
Drug Resistance, Neoplasm
Epithelial Cells
Fatty Acid Desaturases
Fatty Acids, Omega-3
Fatty Acids, Omega-6
Fatty Acids, Unsaturated
Gene Knockdown Techniques
Gene Knockout Techniques
Humans
Inflammation
Male
Mice
Mice, Knockout
Mice, Nude
Mice, Transgenic
Neovascularization, Pathologic
Orchiectomy
PTEN Phosphohydrolase
Prostatic Neoplasms
Proteasome Endopeptidase Complex
Proteolysis
Proto-Oncogene Proteins c-akt
Receptors, Androgen