Investigation of the Effects of Polyunsaturated Fatty Acid Ratios in Human SH-SY5Y Cells by in vitro Methods

INTRODUCTION: Neuroblastoma, an embryonic tumour of the sympathetic nervous system, is the deadliest type of cancer, accounting for 6-9% of all childhood cancers. The ω-6: ω-3=13/1 ratio is associated with the presence of chronic disease, it is reported that reducing this ratio to 7/1 protects against cancer and cardiovascular diseases.


METHODS: This study aims to investigate the anticancer effects of different ratios of ω-3 and ω-6 fatty acids on human neuroblastoma cells (SHSY-5Y). For this purpose, SHSY-5Y cells were treated with different ratios of ω-3 (EPA) and ω-6 (LA) fatty acids for 48 and 72 hours. The viability of ω-3 and ω-6 fatty acid-treated cells was measured by the MTT. The percent of cell apoptosis was detected by the FITC-conjugated Annexin-V/PI assay, and ROS analysis was performed by flow cytometry. The expression levels of TNFα, IL-6, and TGFβ1 genes were studied using RT-PCR.
RESULTS: EPA and LA separately significantly inhibited the proliferation of SH-SY5Y cells within 48 hours (p<0.001). It was found that apoptosis decreased significantly in all groups due to PUFAs application at different ratios, and the most effective dose was ω-3: ω-6 ratio: 1/1. While ROS levels were significantly decreased compared to the control group, the lowest ROS level was observed in the ω-3: ω-6 ratio: 1/4 group. Both TNF-α, IL6, and TGFβ1 mRNA expressions increased significantly after the addition of fatty acid mixtures compared to the control; they were observed to decrease with an increasing ω-6 ratio.
DISCUSSION AND CONCLUSION: Our study is the first to examine the effects of the ω-3: ω-6 ratio on neuroblastoma cancer cells. We observed that the application of omega fatty acids caused a decrease in apoptosis at all ratios. In contrast, when the ω-3: ω-6 ratio increased, there was a decrease in the amount of ROS. Additionally, as the ω-3: ω-6 ratio increases, a decrease in the release of pro-inflammatory cytokines is noted.