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Omega-3 Polyunsaturated Fatty Acids Trigger Cell Cycle Arrest and Induce Apoptosis in Human Neuroblastoma LA-N-1 Cells

Biochemistry Programme, School of Life Sciences, The Chinese University of Hong Kong, Shatin, Hong Kong, China
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Nutrients 2015, 7(8), 6956-6973; https://doi.org/10.3390/nu7085319
Received: 27 June 2015 / Revised: 29 July 2015 / Accepted: 12 August 2015 / Published: 18 August 2015
Omega-3 (n-3) fatty acids are dietary long-chain fatty acids with an array of health benefits. Previous research has demonstrated the growth-inhibitory effect of n-3 fatty acids on different cancer cell lines in vitro, yet their anti-tumor effects and underlying action mechanisms on human neuroblastoma LA-N-1 cells have not yet been reported. In this study, we showed that docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) exhibited time- and concentration-dependent anti-proliferative effect on the human neuroblastoma LA-N-1 cells, but had minimal cytotoxicity on the normal or non-tumorigenic cells, as measured by MTT reduction assay. Mechanistic studies indicated that DHA and EPA triggered G0/G1 cell cycle arrest in LA-N-1 cells, as detected by flow cytometry, which was accompanied by a decrease in the expression of CDK2 and cyclin E proteins. Moreover, DHA and EPA could also induce apoptosis in LA-N-1 cells as revealed by an increase in DNA fragmentation, phosphatidylserine externalization and mitochondrial membrane depolarization. Up-regulation of Bax, activated caspase-3 and caspase-9 proteins, and down-regulation of Bcl-XL protein, might account for the occurrence of apoptotic events. Collectively, our results suggest that the growth-inhibitory effect of DHA and EPA on LA-N-1 cells might be mediated, at least in part, via triggering of cell cycle arrest and apoptosis. Therefore, DHA and EPA are potential anti-cancer agents which might be used for the adjuvant therapy or combination therapy with the conventional anti-cancer drugs for the treatment of some forms of human neuroblastoma with minimal toxicity. View Full-Text
Keywords: apoptosis; cell cycle arrest; docosahexaenoic acid; eicosapentaenoic acid; LA-N-1 cells; neuroblastoma; omega-3 polyunsaturated fatty acids apoptosis; cell cycle arrest; docosahexaenoic acid; eicosapentaenoic acid; LA-N-1 cells; neuroblastoma; omega-3 polyunsaturated fatty acids
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So, W.W.; Liu, W.N.; Leung, K.N. Omega-3 Polyunsaturated Fatty Acids Trigger Cell Cycle Arrest and Induce Apoptosis in Human Neuroblastoma LA-N-1 Cells. Nutrients 2015, 7, 6956-6973.

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