Involvement of apoptotic pathways in docosahexaenoic acid-induced benefit in prostate cancer: Pathway-focused gene expression analysis using RT2Profile PCR Array System.
BACKGROUND
Present study aimed to better understand the potential apoptotic pathways that involved in docosahexaenoic acid (DHA)-induced apoptosis of prostate cancer cells.


METHODS
Human prostate cancer DU145 cells were treated with different concentrations of fish oil, omega-3 PUFA (DHA, and Eicosapentaenoic acid, EPA), or omega-6 PUFA (Arachidonic acid, AA). Cell viability and apoptosis were evaluated by MTT assay and Hoechst staining. Pathway-focused gene expression profiling of DU145 cells was analyzed with the RT2Profile PCR Array System. The results were verified by real time quantitative polymerase chain reaction (RT-qPCR).


RESULTS
AA exposure showed no obvious effect on viability of DU145 cells. However, exposure with fish oil, EPA, or DHA for 24 h significantly affected cell viability. The growth inhibition of DHA was more pronounced than that of EPA and showed a time-dependent increase. DHA exposure caused typical apoptotic characteristics. Ten genes were more expressed, while 5 genes were less expressed following DHA exposure. RT-qPCR confirmed the time dependent effect of DHA on the expression of these differentially expressed genes. KEGG pathway analysis showed that DHA may induce the apoptosis of cancer cells preferentially through mediating P53, MAPK, TNF, PI3K/AKT, and NF-κB signaling pathways.


CONCLUSIONS
Our study demonstrated the beneficial action of DHA on human prostate carcinoma cell line DU145. The pro-apoptotic effect of DHA on DU145 cells may involve mediation various pathways, especially P53, MAPK, TNF, PI3K/AKT, and NF-κB signaling pathways. Molecular mechanisms of DHA on apoptosis of cancer cells still need to be further clarified.
Department of Obstetrics and Gynecology, Bethune International Peace Hospital of the People's Liberation Army, Shijiazhuang, 050082, China.
Yanan
Y
Sun
Department of Urology, The Third Hospital of Hebei Medical University, Shijiazhuang, 050051, China. xiaopengjia71@163.com.
Xiaopeng
X
Jia
Department of Biochemistry and Molecular Biology, Hebei Medical University, Shijiazhuang, 050017, China.
Lianguo
L
Hou
Department of Orthopaedic Trauma, Section II, The Third Hospital of Shijiazhuang City, Shijiazhuang, Hebei, 050011, China.
Xing
X
Liu
Department of Nutrition and Food hygiene, Hebei Medical University, Shijiazhuang, 050017, China.
Qiang
Q
Gao
D017209:Apoptosis / Q000187:drug effects*; D016718:Arachidonic Acid / Q000494:pharmacology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004281:Docosahexaenoic Acids / Q000494:pharmacology*; D015118:Eicosapentaenoic Acid / Q000494:pharmacology*; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D020928:Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism; D011467:Prostate / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D015398:Signal Transduction; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism
D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D016159:Tumor Suppressor Protein p53; D004281:Docosahexaenoic Acids; D016718:Arachidonic Acid; D015118:Eicosapentaenoic Acid; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D020928:Mitogen-Activated Protein Kinases
DU145 cells; Docosahexaenoic acid (DHA); Human prostate carcinoma cell; RT2 profile PCR array system