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
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Young-Min Han1, Migyeung Jeong1, Jong-Min Park1, Mi-Young Kim1,4, Eun-Jin Go1, Ji Young Cha2, Kyung Jo Kim3, Ki Baik Hahm1,4
1CHA Cancer Prevention Research Center, CHA Cancer Institute, CHA University, Seoul, Korea
2Gachon University Lee Gil Ya Cancer and Diabetes Institute, Incheon, Korea
3Department of Gastroenterology, University of Ulsan, Seoul Asan Hospital, Seoul, Korea
4Department of Gastroenterology, CHA Bundang Medical Center, Seongnam, Korea
Ki Baik Hahm, email: [email protected]
Keywords: fat-1 transgenic mice, colitic cancer, COX-2, ω-3 PUFAs, 15-PGDH, β-catenin complex
Received: June 08, 2016 Accepted: August 15, 2016 Published: August 23, 2016
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.
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