Anti-inflammatory effects of docosahexaenoic acid: Implications for its cancer chemopreventive potential

The implication of inflammatory tissue damage in pathophysiology of human cancer as well as some metabolic disorders has been under intense investigation. Numerous studies have identified a series of critical signaling molecules involved in cellular responses to inflammatory stimuli. These include nuclear factor κB, peroxisome proliferator-activated receptor γ, nuclear factor erythroid 2 p45-related factor 2 and sterol regulatory element-binding protein 1. The proper regulation of these transcription factors mediating pro- and anti-inflammatory signaling hence provides an important strategy for the chemoprevention of inflammation-associated cancer. There is compelling evidence supporting that dietary supplementation with fish oil-derived ω-3 polyunsaturated fatty acids including docosahexaenoic acid (DHA) ameliorates symptomatic inflammation associated with cancer as well as other divergent human disorders. Acute or physiologic inflammation is an essential body's first line of defence to microbial infection and tissue injuries, but it must be properly completed by a process termed 'resolution'. Failure of resolution mechanisms can result in persistence of inflammation, leading to chronic inflammatory conditions and related malignancies. The phagocytic engulfment of apoptotic neutrophils and clearance of their potentially histotoxic contents by macrophages, called efferocytosis is an essential component in resolving inflammation. Of note, DHA is a precursor of endogenous proresolving lipid mediators which regulate the leukocyte trafficking and recruitment and thereby facilitate efferocytosis. Therefore, DHA and its metabolites may have a preventive potential in the management of human cancer which arises as a consequence of impaired resolution of inflammation as well as chronic inflammation.