title: The ω-3 polyunsaturated fatty acids prevented colitis-associated carcinogenesis through blocking dissociation of β-catenin complex, inhibiting COX-2 through repressing NF-κB, and inducing 15-prostaglandin dehydrogenase.
abstract: Numerous studies have demonstrated that diets containing an increased ratio of ω-6 : ω-3 polyunsaturated fatty acids (PUFAs) are a risk factor for colon cancer and might affect tumorigenesis. Therefore, dietary ω-3 PUFA administration may be a preventive strategy against colon cancer. Until now, the exact molecular mechanisms and required dietary doses of ω-3 PUFAs for cancer prevention were unknown. In this study, we explored the anti-tumorigenic mechanisms of ω-3 PUFAs against a colitis-associated cancer (CAC) model. Through in vitro cell models involving docosahexaenoic acid (DHA) administration, down-regulation of survivin and Bcl-2, and up-regulation of Bax, accompanied by blockage of β-catenin complex dissociation, the main mechanisms responsible for DHA-induced apoptosis in HCT116 cells were determined. Results included significant reduction in azoxymethane-initiated, dextran sodium sulfate-promoted CACs, as well as significant preservation of 15-hydroxyprostaglandin dehydrogenase (15-PGDH) and significant inhibition of Cyclooxyganase-2 (COX-2) and Prostaglandin E2(P < 0.01). Additional mechanisms and significant induction of apoptosis in both tumor and non-tumor tissues were also noted in fat-1 transgenic (TG) mice. The lipid profiles of colon tissues measured in all specimens revealed that intake greater than 3 g ω-3 PUFA/60 kg of body weight showed tissue levels similar to those seen in fat-1 TG mice, preventing cancer. Our study concluded that COX-2 inhibition, 15-PGDH preservation, apoptosis induction, and blockage of β-catenin complex dissociation contributed to the anti-tumorigenesis effect of ω-3 PUFAs, and an intake higher than 3g ω-3 PUFAs/60 kg of body weight can assist in CAC prevention.
authors: CHA Cancer Prevention Research Center, CHA Cancer Institute, CHA University, Seoul, Korea.
authors: Young-Min
authors: YM
authors: Han
authors: CHA Cancer Prevention Research Center, CHA Cancer Institute, CHA University, Seoul, Korea.
authors: Migyeung
authors: M
authors: Jeong
authors: CHA Cancer Prevention Research Center, CHA Cancer Institute, CHA University, Seoul, Korea.
authors: Jong-Min
authors: JM
authors: Park
authors: CHA Cancer Prevention Research Center, CHA Cancer Institute, CHA University, Seoul, Korea.|Department of Gastroenterology, CHA Bundang Medical Center, Seongnam, Korea.
authors: Mi-Young
authors: MY
authors: Kim
authors: CHA Cancer Prevention Research Center, CHA Cancer Institute, CHA University, Seoul, Korea.
authors: Eun-Jin
authors: EJ
authors: Go
authors: Gachon University Lee Gil Ya Cancer and Diabetes Institute, Incheon, Korea.
authors: Ji Young
authors: JY
authors: Cha
authors: Department of Gastroenterology, University of Ulsan, Seoul Asan Hospital, Seoul, Korea.
authors: Kyung Jo
authors: KJ
authors: Kim
authors: CHA Cancer Prevention Research Center, CHA Cancer Institute, CHA University, Seoul, Korea.|Department of Gastroenterology, CHA Bundang Medical Center, Seongnam, Korea.
authors: Ki Baik
authors: KB
authors: Hahm
mesh_terms: D000818:Animals; D063646:Carcinogenesis / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D049109:Cell Proliferation / Q000187:drug effects; D003092:Colitis / Q000150:complications*; D003110:Colonic Neoplasms / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control*; D051546:Cyclooxygenase 2 / Q000737:chemistry*; D015525:Fatty Acids, Omega-3 / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D006911:Hydroxyprostaglandin Dehydrogenases / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D016328:NF-kappa B / Q000037:antagonists & inhibitors*; D014407:Tumor Cells, Cultured; D051176:beta Catenin / Q000037:antagonists & inhibitors*
chemical_list: D015525:Fatty Acids, Omega-3; D016328:NF-kappa B; D051176:beta Catenin; D006911:Hydroxyprostaglandin Dehydrogenases; C035859:15-hydroxyprostaglandin dehydrogenase; D051546:Cyclooxygenase 2
keywords: 15-PGDH; COX-2; colitic cancer; fat-1 transgenic mice; β-catenin complex; ω-3 PUFAs