Highly unsaturated (n-3) fatty acids, but not alpha-linolenic, conjugated linoleic or gamma-linolenic acids, reduce tumorigenesis in Apc(Min/+) mice

We showed previously that dietary eicosapentaenoic acid [EPA, 20:5(n-3)] is antitumorigenic in the Apc(Min/+) mouse, a genetic model of intestinal tum origenesis. Only a few studies have evaluated the effects of dietary fatty acids, including EPA and docosahexaenoic acid [DHA, 22:6(n-3)], in this ani mal model and none have evaluated the previously touted antitumorigenicity of alpha-linolenic acid [ALA, 18:3(n-3)], conjugated linoleic acid [CLA, 77 % 18:2(n-7)], or gamma-linolenic acid [GLA, 18:3(n-6)]. Stearidonic acid [S DA, 18:4(n-3)], the Delta 6-desaturase product of ALA, which is readily met abolized to EPA, has not been evaluated previously for antitumorigenic effi cacy. This study was undertaken to evaluate the antitumorigenicity of these dietary fatty acids (ALA, SDA, EPA, DHA, CLA and GLA) compared with oleic acid [OA, 18:1(n-9)] at a level of 3 g/100 g in the diets of Apc(Min/+) mic e and to determine whether any alterations in tumorigenesis correspond to a lterations in prostaglandin biosynthesis. Tumor multiplicity was significan tly lower by similar to 50% in mice fed SDA or EPA compared with controls, whereas less pronounced effects were observed in mice fed DHA (P = 0.15). A LA, CLA and GLA were ineffective at the dose tested. Although lower tumor n umbers coincided with significantly lower prostaglandin levels in SDA- and EPA-fed mice, ALA and DHA supplementation resulted in equally low prostagla ndin levels, despite proving less efficacious with regard to tumor number. Prostaglandin levels did not differ significantly in the CLA and GLA groups compared with controls. These results suggest that SDA and EPA attenuate t umorigenesis in this model and that this effect may be related in part to a lterations in prostaglandin biosynthesis.