Omega-3 Polyunsaturated Fatty Acids and Their Bioactive Metabolites in Gastrointestinal Malignancies Related to Unresolved Inflammation. A Review

Abstract

Chronic inflammation takes part in the pathogenesis of some malignancies of the gastrointestinal tract including colorectal (CRC), gastric, and esophageal cancers. The use of ω3 polyunsaturated fatty acid (ω3-PUFA) supplements for chemoprevention or adjuvant therapy of gastrointestinal cancers is being investigated in recent years. Most evidence has been reported in CRC, although their protective role has also been reported for Helicobacter pylori -induced gastric cancer or Barrett’s esophagus-derived adenocarcinoma. Studies based on ω3-PUFA supplementation in animal models of familial adenomatous polyposis (FAP) and CRC revealed positive effects on cancer prevention, reducing the number and size of tumors, down-regulating arachidonic acid-derived eicosanoids, upregulating anti-oxidant enzymes, and reducing lipid peroxidation, whereas contradictory results have been found in induced colitis and colitis-associated cancer. Beneficial effects have also been found in FAP and ulcerative colitis patients. Of special interest is their positive effect as adjuvants on radio- and chemo-sensitivity, specificity, and prevention of treatment complications. Some controversial results obtained in CRC might be justified by different dietary sources, extraction and preparation procedures of ω3-PUFAs, difficulties on filling out food questionnaires, daily dose and type of PUFAs, adenoma subtype, location of CRC, sex differences, and genetic factors. Studies using animal models of inflammatory bowel disease have confirmed that exogenous administration of active metabolites derived from PUFAs called pro-resolving mediators like lipoxin A4, arachidonic acid-derived, resolvins derived from eicosapentaenoic (EPA), docosahexaenoic (DHA), and docosapentaenoic (DPA) acids as well as maresin 1 and protectins DHA- and DPA-derived improve disease and inflammatory outcomes without causing immunosuppression or other side effects.

New Perspectives in the Study of Intestinal Inflammation: Focus on the Resolution of Inflammation

“…Maresins (macrophage mediators in resolving inflammation) are the SPMs first identified in macrophages [ 57 ], but also produced by neutrophils [ 58 ], which are biosynthesised from docosahexaenoic acid (DHA) and by the action of 12-lipoxigenase (12-LOX) into MaR1 and MaR2 [ 19 , 57 , 59 ]. MaR1 is the best-known maresin, and its actions on the resolution of inflammation are well documented in different tissues and diseases [ 16 , 60 ]. Regarding IBD, it has been demonstrated that MaR1 exerted anti-inflammatory and pro-resolving actions in two different animal models of colitis (DSS- and TNBS-induced colitis) [ 61 ].…”

Anemonia sulcata and Its Symbiont Symbiodinium as a Source of Anti-Tumor and Anti-Oxidant Compounds for Colon Cancer Therapy: A Preliminary In Vitro Study

“…In fact, the presence of PUFA (n-6 PUFA, EPA and DHA) in the diet has been correlated with a significant decrease in digestive cancer risk, which may be regulated by the ingestion of vegetables, fruits, vitamin C and fiber [39]. Moreover, PUFAs not only have a protective effect in CRC but also improve its treatment by increasing the activity of antioxidant enzymes, reducing lipid peroxidation and inhibiting harmful derivatives of arachidonic acid, thus warranting their use as adjuvants in radio and chemotherapy [40]. In relation to this last point, the absence of arachidonic acid-which is associated with an increased risk of CRC [38]-in the anemones, both with (W) and without (W/O) its microalgal symbiont, reinforces our hypothesis.…”

The Role of Pro-Resolving Lipid Mediators in Colorectal Cancer-Associated Inflammation: Implications for Therapeutic Strategies

“…Although DPA-derived metabolites, named protectin D1 n−3 DPA (PD1 n−3 DPA ) and resolvin D5 n−3 DPA (RvD5 n−3 DPA ), have been found to suppress chronic inflammation [19,122] and their role in cancer, and CRC has not been elucidated yet. So far, only one study reported that RvD5 may be useful for attenuating chemotherapy-induced peripheral neuropathy (CIPN), a rising health concern in cancer survivors [123].…”