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Omega-3 fatty acid derived endocannabinoids as anticancer agents in breast cancer

Many studies have reported the anti-cancer effects of n-3 long chain polyunsaturated fatty acids (n-3 LCPUFAs). In this study, the anticancer effects of n-3 LCPUFAs and their derivatives, n-3 n-acyl ethanolamides (n-3 NAEs) were investigated in MCF-7 and MDA-MB-231 breast cancer cell lines. The focus was on their effects on cell proliferation, the role of CB1 and CB2 receptors, the effects of their main metabolising enzyme, FAAH, and which molecular signalling pathways are involved. In addition, the effects on the redox system, particularly in the modulation of redox genes, proteins and enzymes, the role of epigenetic regulation, and the effects on cell invasion and migration were also investigated. The results showed that n-3 NAEs were more potent than their parent LCPUFAs at reducing cell viability while the effects of both n-3 LCPUFAs and n-3 NAEs appear to be CB receptor mediated. In addition, MAPK pathways were also affected to varying extents following treatment, in particular p38 and JNK. Furthermore, global methylation, antioxidant gene expression, migration and invasion were in general all modulated by treatment. However, the effects observed were found to be both treatment- and cell- type dependent. Nevertheless, these results confirm that n-3 LCPUFAs and n-3 NAEs inhibit breast cancer cell growth, and modulate important cancer related pathways albeit by different mechanisms. This suggests that dietary intervention with cheap, safe, readily available fatty acids could be introduced to breast cancer patients to enhance treatment.

Identiferoai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:655662
Date January 2015
CreatorsLee, Jisun
PublisherUniversity of Aberdeen
Source SetsEthos UK
Detected LanguageEnglish
TypeElectronic Thesis or Dissertation
Sourcehttp://digitool.abdn.ac.uk:80/webclient/DeliveryManager?pid=225938

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