HPGD and cancer: In vivo study involving azoxymethane (AOM)-initiated, dextran sulfate sodium (DSS)-promoted CACs, along with reporting that fat-1 TG mice showed significantly lower incidence of cancer, we explored the cancer preventive mechanisms of docosahexaenoic acid (DHA), including selective cytotoxicity against colon cancer cells by apoptosis and cell cycle inhibition, blocking the dissociation of β-catenin complex, and induction of tumor suppressive 15-prostaglandin dehydrogenase (15-PGDH), beyond the reported anti-proliferative, anti-inflammatory, and anti-oxidative actions.