Omega 3 but not omega 6 fatty acids inhibit AP-1 activity and cell transformation in JB6 cells

Epidemiological and animal-based investigations have indicated that the dev elopment of skin cancer is in part associated with poor dietary practices. Lipid content and subsequently the derived fatty acid composition of the di et are believed to play a major role in the development of tumorigenesis. O mega 3 (omega3) fatty acids, including docosahexaenoic acid (DHA) and eicos apentaenoic acid (EPA), can effectively reduce the risk of skin cancer wher eas omega 6 (omega6) fatty acids such as arachidonic acid (AA) reportedly p romote risk. To investigate the effects of fatty acids on tumorigenesis. we performed experiments to examine the effects of the w3 fatty acids EPA and DHA and of the w6 fatty acid AA on phorbol 12-tetradecanoate 13-acetate (T PA)-induced or epidermal growth factor (EGF)-induced transcription activato r protein 1 (AP-1) transactivation and on the subsequent cellular transform ation in a mouse epidermal JB6 cell model. DHA treatment resulted in marked inhibition of TPA- and ECF-induced cell transformation by inhibiting AP-1 transactivation. EPA treatment also inhibited TPA-induced AP-1 transactivat ion and cell transformation but had no effect on EGF-induced transformation . AA treatment had no effect on either TPA- or EGF-induced AP-1 transactiva tion or transformation, but did abrogate the inhibitory effects of DHA on T PA- or ECF-induced AP-1 transactivation and cell transformation in a dose-d ependent manner. The results of this study demonstrate that the inhibitory effects of omega3 fatty acids on tumorigenesis are more significant for DHA than for EPA and are related to an inhibition of AP-1. Similarly, because AA abrogates the beneficial effects of DHA. the dietary ratio of omega6 to omega3 fatty acids may be a significant factor in mediating tumor developme nt.