Abstract
OBJECTIVES: Neuroblastoma, an embryonic tumor of the sympathetic nervous system, is the deadliest type of cancer, accounting for 6-9% of all childhood cancers. The omega (ω)-6 [linoleic acid (LA)]: ω-3 [eicosapentaenoic acid (EPA)]=13/1 ratio is associated with the presence of chronic disease, and it has been reported that reducing this ratio to 7/1 protects against cancer and cardiovascular diseases. This study aimed to investigate the anticancer effects of different ratios of ω-3 and ω-6 fatty acids in human neuroblastoma cells (SHSY-5Y). MATERIALS AND METHODS: SHSY-5Y cells were treated with different ratios of ω-3 and ω-6 fatty acids for 48 and 72 h. The viability of ω-3 and ω-6 fatty acid-treated cells was measured using the methylthiazolyldiphenyl-tetrazolium bromide. The percentage of cell apoptosis was detected using the Fluorescein Isothiocyanate-conjugated Annexin-V/PI assay, and reactive oxygen species (ROS) analysis was performed using flow cytometry. The expression levels of tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and transforming growth factor beta 1 (TGFβ1) genes were determined using real-time polymerase chain reaction. RESULTS: EPA and LA separately significantly inhibited the proliferation of SH-SY5Y cells within 48 h (p<0.001). It was found that apoptosis decreased significantly in all groups due to the application of polyunsaturated fatty acids at different ratios, and the most effective dose was ω-3:ω-6 ratio: 1/1. ROS levels were significantly decreased compared with the control group and the lowest ROS level was observed in the ω-3:ω-6 ratio: 1/4 group. Both TNF-α, IL-6, and TGFβ1 mRNA expressions increased significantly after the addition of fatty acid mixtures compared with the control; they were observed to decrease with an increasing ω-6 ratio. CONCLUSION: This study is the first to examine the effects of the ω-3:ω-6 ratio on neuroblastoma cancer cells. The application of ω fatty acids decreased apoptosis at all ratios. In contrast, when the ω-3: ω-6 ratio increased, the amount of ROS. Additionally, as the ω-3:ω-6 ratio increases, a decrease in the release of pro-inflammatory cytokines is noted.