Document Type
Article
Publication Date
2014
College/Unit
School of Pharmacy
Department/Program/Center
Pharmaceutical Sciences
Abstract
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.
Digital Commons Citation
Chen, Jianchu; Creed, Ashley; Chen, Allen Y.; Huang, Haizhi; Li, Zhaoliang; Rankin, Gary O.; Ye, Xingqian; Xu, Guihua; and Chen, Yi C., "Nobiletin suppresses cell viability through AKT Pathways in PC-3 and DU-145 prostate cancer cells" (2014). Faculty & Staff Scholarship. 2482.
https://researchrepository.wvu.edu/faculty_publications/2482
Source Citation
Chen, J., Creed, A., Chen, A.Y. et al. Nobiletin suppresses cell viability through AKT Pathways in PC-3 and DU-145 prostate cancer cells. BMC Pharmacol Toxicol 15, 59 (2014). https://doi.org/10.1186/2050-6511-15-59
Comments
This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.