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

So WW, Liu WN, Leung KN - Nutrients (2015)

Bottom Line: Omega-3 (n-3) fatty acids are dietary long-chain fatty acids with an array of health benefits.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.

View Article: PubMed Central - PubMed

Affiliation: Biochemistry Programme, School of Life Sciences, The Chinese University of Hong Kong, Shatin, Hong Kong, China. timothyso30@hotmail.com.

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.

No MeSH data available.


Related in: MedlinePlus

DHA and EPA induce DNA fragmentation in LA-N-1 cells. LA-N-1 cells were treated with various concentrations of DHA (A) or EPA (B) for 72 hours. Cells treated with ethanol acted as the control. After incubation, the occurrence of DNA fragmentation was detected by the Cell Death Detection ELISAPLUS Kit. The results represent mean enrichment factor ± SD of quadruplicate measurements. ** p < 0.01, *** p < 0.001.
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nutrients-07-05319-f003: DHA and EPA induce DNA fragmentation in LA-N-1 cells. LA-N-1 cells were treated with various concentrations of DHA (A) or EPA (B) for 72 hours. Cells treated with ethanol acted as the control. After incubation, the occurrence of DNA fragmentation was detected by the Cell Death Detection ELISAPLUS Kit. The results represent mean enrichment factor ± SD of quadruplicate measurements. ** p < 0.01, *** p < 0.001.

Mentions: Apoptosis is a well-regulated process with several key events, one of which is the induction of DNA fragmentation in the cells [27]. To examine whether DHA or EPA could trigger DNA fragmentation in LA-N-1 cells, the Cell Death Detection ELISAPLUS Kit was used according to manufacturer’s instruction. As shown in Figure 3, DHA and EPA could induce DNA fragmentation in LA-N-1 cells in a concentration-dependent manner as reflected by an increase in the enrichment factor.


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

So WW, Liu WN, Leung KN - Nutrients (2015)

DHA and EPA induce DNA fragmentation in LA-N-1 cells. LA-N-1 cells were treated with various concentrations of DHA (A) or EPA (B) for 72 hours. Cells treated with ethanol acted as the control. After incubation, the occurrence of DNA fragmentation was detected by the Cell Death Detection ELISAPLUS Kit. The results represent mean enrichment factor ± SD of quadruplicate measurements. ** p < 0.01, *** p < 0.001.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4555158&req=5

nutrients-07-05319-f003: DHA and EPA induce DNA fragmentation in LA-N-1 cells. LA-N-1 cells were treated with various concentrations of DHA (A) or EPA (B) for 72 hours. Cells treated with ethanol acted as the control. After incubation, the occurrence of DNA fragmentation was detected by the Cell Death Detection ELISAPLUS Kit. The results represent mean enrichment factor ± SD of quadruplicate measurements. ** p < 0.01, *** p < 0.001.
Mentions: Apoptosis is a well-regulated process with several key events, one of which is the induction of DNA fragmentation in the cells [27]. To examine whether DHA or EPA could trigger DNA fragmentation in LA-N-1 cells, the Cell Death Detection ELISAPLUS Kit was used according to manufacturer’s instruction. As shown in Figure 3, DHA and EPA could induce DNA fragmentation in LA-N-1 cells in a concentration-dependent manner as reflected by an increase in the enrichment factor.

Bottom Line: Omega-3 (n-3) fatty acids are dietary long-chain fatty acids with an array of health benefits.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.

View Article: PubMed Central - PubMed

Affiliation: Biochemistry Programme, School of Life Sciences, The Chinese University of Hong Kong, Shatin, Hong Kong, China. timothyso30@hotmail.com.

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.

No MeSH data available.


Related in: MedlinePlus