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

Wai So,Kwok Leung,Wai Liu

doi:10.3390/nu7085319

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.

Highlights

Neuroblastoma is the second most common extracranial malignant tumor of childhood and the most common solid tumor of infancy arising from neural crest cells, which can be developed anywhere in the sympathetic nervous system [1]
Due to the relatively higher potency of docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) with respect to their anti-proliferative effect on LA-N-1 cells, they were chosen to be the specific targets for further mechanistic studies
We found that there was a decrease in the protein expression levels of CDK2 and cyclin E in the DHA- or EPA-treated LA-N-1 cells, indicating that the growth-inhibitory effect of DHA

Summary

Introduction

Neuroblastoma is the second most common extracranial malignant tumor of childhood and the most common solid tumor of infancy arising from neural crest cells, which can be developed anywhere in the sympathetic nervous system [1]. It accounts for around 8%–10% of all childhood cancers and about 15% of cancer deaths in children [1]. Current treatment of neuroblastoma depends on the risk categories of the patients Those who suffer from low- and intermediate-risk neuroblastoma can be treated with surgery and low dose chemotherapy without radiotherapy, and the survival rate is satisfactory [3,4]. There is a pressing need to develop some novel agents, especially those derived from natural products, which are more efficacious to inhibit the proliferation of cancer cells while exerting minimal cytotoxicity towards normal cells, as an alternative strategy in neuroblastoma treatment

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Conclusion