Minimizing Membrane Arachidonic Acid Content as a Strategy for Controlling Cancer: A Review

Many cancers and pre-cancerous lesions convert membrane-bound arachidonic acid (AA) to eicosanoids that promote the survival, growth, and spread of cancer. In contrast, the long-chain omega-3s eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) can competitively inhibit AA's interaction with the enzymes that give rise to eicosanoids, while acting as precursors for alternative eicosanoids which oppose cancer development and growth. Hence, minimizing the AA content of cancer membranes, while boosting that of EPA and DHA, is a rational strategy for cancer prevention and control. The former goal can be achieved by eating a plant-based diet (inherently free of AA); by avoiding foods high in linoleic acid; by down-regulating the expression of delta-6-desaturase (D6D), rate-limiting for the conversion of linoleic acid to AA; and by competitively decreasing flux of linoleic acid through D6D with a high intake of alpha-linolenic acid (ALA) from flaxseed. ALA and DHA, potent agonists for the farnesoid X receptor, can be expected to suppress D6D transcription, and AMP-activated kinase (AMPK) activators and a cholesterol-free diet also have potential in this regard. Hence, a plant-based diet low in linoleic acid, complemented by an ample intake of flaxseed and supplemental fish oil, with or without metformin and other D6D-antagonist agents, may aid prevention and control of some cancers.