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

Hu,Zhimei; Qi,Haixia; Zhang,Ruixue; Zhang,Kun; Shi,Zhemin; Chang,Yanan; Chen,Linfeng; Esmaeili,Mohsen; Baniahmad,Aria; Hong,Wei

doi:10.3892/mmr.2015.3813

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

Authors:
- Zhimei Hu
- Haixia Qi
- Ruixue Zhang
- Kun Zhang
- Zhemin Shi
- Yanan Chang
- Linfeng Chen
- Mohsen Esmaeili
- Aria Baniahmad
- Wei Hong
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Affiliations: Department of Histology and Embryology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin 300070, P.R. China, Department of Medical Oncology, Harvard Medical School, Dana Farber Cancer Institute, Boston, MA 02115, USA, Institute of Human Genetics, Jena University Hospital, Jena D‑07740, Germany
Published online on: May 21, 2015 https://doi.org/10.3892/mmr.2015.3813
Pages: 3769-3774

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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.

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