Omega-3 Polyunsaturated Fatty Acids Trigger Cell Cycle Arrest and Induce Apoptosis in Human Neuroblastoma LA-N-1 Cells
Autor: | Wai Wing So, Wai Nam Liu, Kwok Nam Leung |
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Rok vydání: | 2015 |
Předmět: |
eicosapentaenoic acid
Cell cycle checkpoint Docosahexaenoic Acids bcl-X Protein Down-Regulation lcsh:TX341-641 Antineoplastic Agents DNA Fragmentation Biology apoptosis cell cycle arrest docosahexaenoic acid LA-N-1 cells neuroblastoma omega-3 polyunsaturated fatty acids Article Neuroblastoma Bcl-2-associated X protein Cell Line Tumor Humans bcl-2-Associated X Protein Nutrition and Dietetics Caspase 3 HEK 293 cells Cell Cycle Checkpoints Eicosapentaenoic acid Caspase 9 Up-Regulation Cell biology HEK293 Cells Apoptosis Docosahexaenoic acid Cancer research biology.protein DNA fragmentation lipids (amino acids peptides and proteins) lcsh:Nutrition. Foods and food supply G1 phase Food Science |
Zdroj: | Nutrients Nutrients; Volume 7; Issue 8; Pages: 6956-6973 Volume 7 Issue 8 Pages 6956-6973 Nutrients, Vol 7, Iss 8, Pp 6956-6973 (2015) |
ISSN: | 2072-6643 |
DOI: | 10.3390/nu7085319 |
Popis: | 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. |
Databáze: | OpenAIRE |
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