Dietary long-chain n−3 fatty acids for the prevention of cancer: a review of potential mechanisms

Abstract

Increasing evidence from animal and in vitro studies indicates that n-3 fatty acids, especially the long-chain polyunsaturated fatty acids eicosapentaenoic acid and docosahexaenoic acid, present in fatty fish and fish oils inhibit carcinogenesis. The epidemiologic data on the association between fish consumption, as a surrogate marker for n-3 fatty acid intake, and cancer risk are, however, somewhat less consistent. This review highlights current knowledge of the potential mechanisms of the anticarcinogenic actions of n-3 fatty acids. Moreover, a possible explanation of why some epidemiologic studies failed to find an association between n-3 fatty acid intake and cancer risk is provided. Several molecular mechanisms whereby n-3 fatty acids may modify the carcinogenic process have been proposed. These include suppression of arachidonic acid-derived eicosanoid biosynthesis; influences on transcription factor activity, gene expression, and signal transduction pathways; alteration of estrogen metabolism; increased or decreased production of free radicals and reactive oxygen species; and mechanisms involving insulin sensitivity and membrane fluidity. Further studies are needed to evaluate and verify these mechanisms in humans to gain more understanding of the effects of n-3 fatty acid intake on cancer risk.

Opposing associations of serum n‐3 and n‐6 polyunsaturated fatty acids with colorectal adenoma risk: An endoscopy‐based case–control study

“…Although there were indications for opposing associations of n-3 and n-6 PUFA on colorectal cancer risk in animal studies, 2,3,8,9 other human studies on colorectal cancer have not found this simultaneous opposing effects of n-3 and n-6 PUFA. [4][5][6]10,[12][13][14] It is hypothesized that n-3 and n-6 PUFA can have opposing effects on colorectal tumor formation via modulation of the AA pathway; by changing the substrates and products, like eicosanoids, or by a direct effect on the genes involved in this pathway, although the precise mechanisms are far from clear.…”

Inhibition of arachidonic acid metabolism and its implication on cell proliferation and tumour-angiogenesis

“…In addition, recent studies were able to assign its therapeutic properties to a marked increase in production of 13S-HODE as well as inhibition of protein kinase C (PKC)-and NADPH-mediated activation of NF-κB and ROS production respectively [154]. Intriguingly, a number of publications can be found suggesting both increased and decreased production of free radicals and ROS to be the reason for modification of carcinogenic processes by omega-3 [ 155 ]. Furthermore, omega-3 supplementation was reported to significantly reduce synthesis of pro-inflammatory 5-LOX metabolites LTA 4 and lipid peroxides, thereby inhibiting IL-1β and TNF-α release [156].…”

The relevance of serum levels of long chain omega-3 polyunsaturated fatty acids and prostate cancer risk: A Meta-analysis

“…These mechanisms of n-3 PUFA regulate inflammation via the eicosanoid pathway [1][2][3][4] and modify androgen production. 5 In particular, dietary intake of long-chain n-3 PUFA or its individual components (eicosapentaenoic acid [EPA], docosahexaenoic acid [DHA], docosapentaenoic acid [DPA]), have been proposed to have an association with prostate cancer risk; however, these results have been inconsistent, largely variable and heterogeneous. [6][7][8][9] These inconsistent results were mainly due to research variations in dietary assessment techniques and under-or overreporting of values, which decreased the accuracy of measuring individual's fatty acid intake.…”