Nobiletin suppresses cell viability through AKT Pathways in PC-3 and DU-145 prostate cancer cells

BMC Clinical Pharmacology

Yi Charlie Chen³  Guihua Xu⁴  Xingqian Ye⁴  Gary O Rankin²  Zhaoliang Li³  Haizhi Huang³  Allen Y Chen¹  Ashley Creed³  Jianchu Chen³ 

[1] Department of Pharmaceutical Science, West Virginia University, Morgantown, WV 26506, USA;Department of Pharmacology, Physiology and Toxicology, Joan C. Edwards School of Medicine, Marshall University, Huntington, WV 25755, USA;College of Science, Technology and Mathematics, Alderson Broaddus University, Philippi, WV 26416, USA;College of Biosystems Engineering and Food Science, Fuli Institute of Food Science, Zhejiang Key Laboratory for Agro-Food Processing, Zhejiang University, Hangzhou 310058, China

关键词: cMyc;    HIF-1α;    NF-κB;    VEGF;    Prostate cancer;    Nobiletin;   

Others  :  1084648
DOI  :  10.1186/2050-6511-15-59

 received in 2014-06-06, accepted in 2014-10-14,  发布年份 2014

【 摘 要 】

Background

Nobiletin is a non-toxic dietary flavonoid that possesses anti-cancer properties. Nobiletin has been reported to reduce the risk of prostate cancer, but the mechanism is not well understood. In this study, we investigated the effects of nobiletin in prostate cancer cell lines PC-3 and DU-145.

Methods

Nobiletin was isolated from a polymethoxy flavonoid mixture using HPLC, cell viability was analyzed with MTS-based assays. Protein expression was examined by ELISA and western blotting. Gene expression was examined by luciferase assay. And the pathways were examined by manipulating genetic components with plasmid transfection.

Results

Data showed that nobiletin decreased cell viability in both prostate cell lines, with a greater reduction in viability in PC-3 cells. HIF-1α expression and AKT phosphorylation were decreased in both cell lines. The VEGF expression was inhibited in PC-3 but not DU-145 cells. cMyc expression was decreased in DU-145 cells. Nobiletin down-regulated NF-κB (p50) expression in nuclei of DU145 cells but not whole cells. It also suppressed NF-κB expression in both whole cells and nuclei of PC-3 cells. Increasing HIF-1α levels reversed nobiletin’s inhibitory effects on VEGF expression, and up-regulating AKT levels reversed its inhibitory effects on HIF-1α expression. We speculate that AKT influences cell viability probably by its effect on NF-κB in both prostate cells. The effect of nobiletin on VEGF expression in PC-3 cell lines was through the AKT/HIF-1α pathway.

Conclusion

Taken together, our results show that nobiletin suppresses cell viability through AKT pathways, with a more profound effect against the more metastatic PC-3 line. Due to this enhanced action against a more malignant cell type, nobiletin may be used to improve prostate cancer survival rates.

【 授权许可】

   
2014 Chen et al.; licensee BioMed Central Ltd.

【 图 表 】

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