Immunomodulatory properties of omega-3 fatty acids: a possible explanation for their systemic, anti-carcinogenic effects.

The recent article by Zapata-Gonzalez et al. [1] was highly interesting. The authors have clearly demonstrated the immunomodulatory effects of docosahexaenoic acid on dendritic cells. Data from recent clinical studies suggest that omega-3 fatty acids exhibit potent, anti-carcinogenic properties. I personally believe that immunomodulation has a major role to play in these systemic, anti-carcinogenic effects exhibited by omega-3 fatty acids. The findings of Zapata-Gonzalez et al. [1] may very well explain these anti-tumerogenic effects of omega-3 fatty acids in various systemic tissues. For instance, Hall et al. [2] have shown that omega-3 fatty acids decrease the risk for colorectal cancer. Similarly, a dietary increase in omega-3 fatty acids, resulting in increased tissue levels of eicosapentaenoic acid, results in an accentuated response to hormone ablation therapy in prostate cancer cells [3]. In fact, Mina [4] has shown that consumption of preserved fish, rich in omega-3 fatty acids, may prevent the evolution and development of prostate carcinomas. Similarly, eicosapentaenoic acid attenuates proliferation in pancreatic tissue by altering angiogenesis by decreasing the expression of cyclooxygenase-2 (COX2) [5]. In fact, omega fatty acids are even effective in inducing apoptosis in chemo-resistant pancreatic carcinomatous tissue [6]. Omega-3 fatty acids also inhibit growth in choloangiocarcinoma cells by accentuated expression of the natural COX2 antagonist, 15-hydroxyprostaglandin dehydrogenase [7]. Similarly, omega-3 fatty acids demonstrate antiproliferative effects in breast carcinomas, secondary to up-regulation of syndecan-1 and activation of the peroxisome proliferator-activated receptor [8]. A similar delay in growth is seen in gastric carcinoma tissue when omega-3 fatty acids are administered in conjunction with a ketogenic diet [9]. Gastric tumors exposed to this combination demonstrate necrotic regions, which are significantly bigger than similar regions in tumors exposed to diets lacking in omega-3 fatty acids. Also, omega-3 fatty acids decrease the expression of matrix metalloproteinase-9 (MMP-9) in keratinocytes and thus, may have a potential role in the management of dermatologic malignancies [10]. Interestingly, the antiproliferative effects of omega-3 fatty acids are in sharp contrast to the proproliferative effects of omega-6 polyunsaturated fatty acids noticed in certain tumors [11]. Omega-3 fatty acids exert these anti-carcinogenic effects by influencing a number of other pathways besides those mentioned above. For instance, part of this antiproliferative effect is secondary to the anti-inflammatory properties of omega-3 fatty acids [12]. In addition, omega-3 fatty acids administration results in increased expression of the tissue inhibitor of MMP-1 along with a simultaneous, decreased expression of metalloproteinases such as MMP-8 that have been implicated in the evolution of a number of systemic malignancies [13]. Tumors exposed to omega-3 fatty acids also exhibit decreased vascularity [9]. Fish oil rich in omega-3 fatty acids may also have a role to play in the management of malignancy-related cachexia [14]. Dietary supplementation of omega-3 fatty acids also attenuates the adverse effects secondary to chemotherapy and radiotherapy. Clearly, omega-3 fatty acids have a major role to play in inhibiting the growth and evolution of multiple different systemic malignancies besides colon carcinoma. Further, largescale studies are needed to detect similar associations between omega-3 fatty acids and other tumors and hopefully, increase the regular use of omega-3 fatty acids as an adjunctive treatment in the management of these systemic malignancies.