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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
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...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Impact Journals LLC
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5325387/ https://www.ncbi.nlm.nih.gov/pubmed/27566583 http://dx.doi.org/10.18632/oncotarget.11544 |
Sumario: | 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 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 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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