title: Docosahexaenoic acid inhibits the growth of hormone-dependent prostate cancer cells by promoting the degradation of the androgen receptor.
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.
authors.affiliation: Department of Histology and Embryology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin 300070, P.R. China.
authors.forename: Zhimei
authors.initials: Z
authors.lastname: Hu
authors.affiliation: Department of Histology and Embryology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin 300070, P.R. China.
authors.forename: Haixia
authors.initials: H
authors.lastname: Qi
authors.affiliation: Department of Histology and Embryology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin 300070, P.R. China.
authors.forename: Ruixue
authors.initials: R
authors.lastname: Zhang
authors.affiliation: Department of Histology and Embryology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin 300070, P.R. China.
authors.forename: Kun
authors.initials: K
authors.lastname: Zhang
authors.affiliation: Department of Histology and Embryology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin 300070, P.R. China.
authors.forename: Zhemin
authors.initials: Z
authors.lastname: Shi
authors.affiliation: Department of Histology and Embryology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin 300070, P.R. China.
authors.forename: Yanan
authors.initials: Y
authors.lastname: Chang
authors.affiliation: Department of Medical Oncology, Harvard Medical School, Dana Farber Cancer Institute, Boston, MA 02115, USA.
authors.forename: Linfeng
authors.initials: L
authors.lastname: Chen
authors.affiliation: Institute of Human Genetics, Jena University Hospital, Jena D‑07740, Germany.
authors.forename: Mohsen
authors.initials: M
authors.lastname: Esmaeili
authors.affiliation: Institute of Human Genetics, Jena University Hospital, Jena D‑07740, Germany.
authors.forename: Aria
authors.initials: A
authors.lastname: Baniahmad
authors.affiliation: Department of Histology and Embryology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin 300070, P.R. China.
authors.forename: Wei
authors.initials: W
authors.lastname: Hong
mesh_terms: D000728:Androgens / Q000235:genetics / Q000378:metabolism; D000970:Antineoplastic Agents / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D004281:Docosahexaenoic Acids / Q000494:pharmacology*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D008297:Male; D011467:Prostate / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D059748:Proteolysis / Q000187:drug effects*; D011944:Receptors, Androgen / Q000235:genetics / Q000378:metabolism*
chemical_list: C410798:AR protein, human; D000728:Androgens; D000970:Antineoplastic Agents; D011944:Receptors, Androgen; D004281:Docosahexaenoic Acids