Investigating the possible mechanisms and gender effects of Omega-3 fatty acids on neuroblastoma, breast and prostate cancers

Abstract

Cancer is a worldwide disease characterised by uncontrollable cell division and tumour growth making it a leading cause of death worldwide. The use of dietary products such a poly-unsaturated fatty acids (PUFAs) to reduce cancer growth is a current area of interest in research. Docosahexaenoic acid (DHA), Alpha-linolenic acid (ALA) and Arachidonic acid (AA) are examples of omega-3 and omega-6 fatty acids found to play a role in carcinogenesis, for example DHA has previously been shown to induce apoptosis in cancer cells without influencing healthy cells. In neuroblastoma cancer development has been delayed by DHA treatment as a result of in vitro mechanisms involving intracellular peroxidation. A further protective effect of omega-3 fatty acids was found in breast cancer patients following high fish consumption and in prostate cancer development the role of omega-3 fatty acids have been highlighted in animal studies, though the later remains a conflicted area of research. Both prostate and breast cancers are gender specific and influenced by hormones, therefore the success of treatments in both these cancers may elicit gender differences. For this reason, neuroblastoma, breast and prostate cancer cell lines have been investigated in the current research to see if PUFAs or gender effects play a role in cancer development. The supplementation of DHA, ALA and AA were investigated across the three cancer cell lines (SH-SY5Y neuroblastoma, MCF-7 breast, PC-3 prostate) using a dose range of 0-1000?M to produce dose-response curves displaying the effects on cell viability. A concentration of 800?M was found to produce an optimal reduction in cell viability across the three cell lines. DHA was found to decrease cell viability of all three cells lines following 24hr and 48hr treatment periods. In this study antagonists of calcium-independent phospholipase A2 (iPLA2), G-protein coupled receptor 40 (GPR40), retinoid-X-receptor (RxR) and nuclear receptors (NR) (bexarotene, tamoxifen, mifepristone, nilutamide) were investigated as pharmacological targets to see if these specific receptors were involved in PUFA effects on cancer cell viability. The antagonists investigated had differing effects on the different cell lines, with certain antagonists eliciting significant cell viability differences in select cell lines. iPLA2 antagonists acting on the SH-SY5Y and MCF-7 lines whereas RxR induced changes in cell viability across all the cell lines. In conclusion, this research has shown IPLA2, GRP40, RxR and nuclear receptors all have an involvement across the three cancer cell lines (SH-SY5Y, MCF-7, PC-3) by significantly affecting cell viability. The prostate cancer cell line did not respond as well to PUFA treatment when compared to the other two cell lines suggesting there may be gender differences, which is in line with previous research displaying no consistent evidence. This research supports the role of PUFAs in prevention and causation of neuroblastoma, breast and prostate cancer.