title: Omega-3 Polyunsaturated Fatty Acids Trigger Cell Cycle Arrest and Induce Apoptosis in Human Neuroblastoma LA-N-1 Cells.
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.
authors: Biochemistry Programme, School of Life Sciences, The Chinese University of Hong Kong, Shatin, Hong Kong, China. timothyso30@hotmail.com.
authors: Wai Wing
authors: WW
authors: So
authors: Biochemistry Programme, School of Life Sciences, The Chinese University of Hong Kong, Shatin, Hong Kong, China. liuwainam0305@hotmail.com.
authors: Wai Nam
authors: WN
authors: Liu
authors: Biochemistry Programme, School of Life Sciences, The Chinese University of Hong Kong, Shatin, Hong Kong, China. knleung@cuhk.edu.hk.
authors: Kwok Nam
authors: KN
authors: Leung
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000235:genetics / Q000378:metabolism; D053453:Caspase 9 / Q000235:genetics / Q000378:metabolism; D059447:Cell Cycle Checkpoints / Q000187:drug effects*; D045744:Cell Line, Tumor; D053938:DNA Fragmentation / Q000187:drug effects; D004281:Docosahexaenoic Acids / Q000494:pharmacology*; D015536:Down-Regulation; D015118:Eicosapentaenoic Acid / Q000494:pharmacology*; D057809:HEK293 Cells; D006801:Humans; D009447:Neuroblastoma / Q000473:pathology; D015854:Up-Regulation; D051028:bcl-2-Associated X Protein / Q000235:genetics / Q000378:metabolism; D051020:bcl-X Protein / Q000235:genetics / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; C494826:BAX protein, human; C494811:BCL2L1 protein, human; D051028:bcl-2-Associated X Protein; D051020:bcl-X Protein; D004281:Docosahexaenoic Acids; D015118:Eicosapentaenoic Acid; C505407:CASP3 protein, human; C506433:CASP9 protein, human; D053148:Caspase 3; D053453:Caspase 9
keywords: LA-N-1 cells; apoptosis; cell cycle arrest; docosahexaenoic acid; eicosapentaenoic acid; neuroblastoma; omega-3 polyunsaturated fatty acids