The omega-3 polyunsaturated fatty acids prevented colitis-associated carcinogenesis through blocking dissociation of beta-catenin complex, inhibiting COX-2 through repressing NF-kappa B, and inducing 15-prostaglandin dehydrogenase
- Authors
- Han, Young-Min; Jeong, Migyeung; Park, Jong-Min; Kim, Mi-Young; Go, Eun-Jin; Cha, Ji Young; Kim, Kyung Jo; Hahm, Ki Baik
- Issue Date
- 27-Sep-2016
- Publisher
- IMPACT JOURNALS LLC
- Keywords
- fat-1 transgenic mice; colitic cancer; COX-2; omega-3 PUFAs; 15-PGDH; beta-catenin complex
- Citation
- ONCOTARGET, v.7, no.39, pp.63583 - 63595
- Journal Title
- ONCOTARGET
- Volume
- 7
- Number
- 39
- Start Page
- 63583
- End Page
- 63595
- URI
- https://scholarworks.bwise.kr/gachon/handle/2020.sw.gachon/7875
- DOI
- 10.18632/oncotarget.11544
- ISSN
- 1949-2553
- Abstract
- Numerous studies have demonstrated that diets containing an increased ratio of omega-6 : omega-3 polyunsaturated fatty acids ( PUFAs) are a risk factor for colon cancer and might affect tumorigenesis. Therefore, dietary omega-3 PUFA administration may be a preventive strategy against colon cancer. Until now, the exact molecular mechanisms and required dietary doses of -3 PUFAs for cancer prevention were unknown. In this study, we explored the anti-tumorigenic mechanisms of omega-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 beta-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 sulfatepromoted CACs, as well as significant preservation of 15-hydroxyprostaglandin dehydrogenase (15-PGDH) and significant inhibition of Cyclooxyganase-2 (COX-2) and Prostaglandin E-2 (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 omega-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 COX2 inhibition, 15-PGDH preservation, apoptosis induction, and blockage of beta-catenin complex dissociation contributed to the anti-tumorigenesis effect of omega-3 PUFAs, and an intake higher than 3g omega-3 PUFAs/60 kg of body weight can assist in CAC prevention.
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