RRC ID 67294
Author So WW, Liu WN, Leung KN.
Title Omega-3 Polyunsaturated Fatty Acids Trigger Cell Cycle Arrest and Induce Apoptosis in Human Neuroblastoma LA-N-1 Cells.
Journal Nutrients
Abstract 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.
Volume 7(8)
Pages 6956-73
Published 2015-8-18
DOI 10.3390/nu7085319
PII nu7085319
PMID 26295255
PMC PMC4555158
MeSH Antineoplastic Agents / pharmacology Apoptosis / drug effects* Caspase 3 / genetics Caspase 3 / metabolism Caspase 9 / genetics Caspase 9 / metabolism Cell Cycle Checkpoints / drug effects* Cell Line, Tumor DNA Fragmentation / drug effects Docosahexaenoic Acids / pharmacology* Down-Regulation Eicosapentaenoic Acid / pharmacology* HEK293 Cells Humans Neuroblastoma / pathology Up-Regulation bcl-2-Associated X Protein / genetics bcl-2-Associated X Protein / metabolism bcl-X Protein / genetics bcl-X Protein / metabolism
IF 4.546
Human and Animal Cells LA-N-1(RCB0483)