Renato Heidor1,2,3, Aline de Conti4, Juliana F Ortega1, Kelly S Furtado1,2, Roberta C Silva5, Paulo E L M Tavares1, Eduardo Purgatto6,2,3, Juliana N R Ract5, Sérgio A R de Paiva7,3, Luiz A Gioielli5, Igor P Pogribny4, Fernando S Moreno1,2,3. 1. Laboratory of Diet, Nutrition and Cancer, Department of Food and Experimental Nutrition, Faculty of Pharmaceutical Sciences, University of São Paulo, São Paulo, Brazil. 2. Advanced Research Center in Food Science and Nutrition (NAPAN), Faculty of Pharmaceutical Sciences, University of São Paulo, Brazil. 3. Food Research Center (FORC), Faculty of Pharmaceutical Sciences, University of São Paulo, Brazil. 4. Division of Biochemical Toxicology, National Center for Toxicological Research, Jefferson, AR, USA. 5. Department of Biochemical and Pharmaceutical Technology, Faculty of Pharmaceutical Sciences, University of São Paulo, São Paulo, Brazil. 6. Laboratory of Food Chemistry and Biochemistry, Department of Food and Experimental Nutrition, Faculty of Pharmaceutical Sciences, University of São Paulo, Brazil. 7. Department of Internal Medicine, Botucatu Medical School, UNESP - São Paulo State University, Botucatu, Brazil.
Abstract
SCOPE: Emerging evidence indicates that the use of bioactive food components is a promising strategy to prevent the development of liver cancer. The goal of this study was to examine the chemopreventive effect of butyrate-containing structured lipids (STLs) produced by an enzymatic interesterification of tributyrin and flaxseed oil on rat hepatocarcinogenesis. METHODS AND RESULTS: Male Wistar rats were subjected to a classic "resistant hepatocyte" model of liver carcinogenesis and treated with STLs, tributyrin or flaxseed oil during the initial phases of hepatocarcinogenesis. Treatment with STLs and tributyrin strongly inhibited the development of preneoplastic liver lesions. The chemopreventive activity of tributyrin was associated with the induction of apoptosis and reduction of the expression of major activated hepatocarcinogenesis-related oncogenes. Treatment with STLs caused substantially greater inhibitory effects than tributyrin on oncogene expression. CONCLUSION: These results demonstrate that the tumor-suppressing activity of butyrate-containing STLs is associated with its ability to prevent and inhibit activation of major hepatocarcinogenesis-related oncogenes. Enrichment of histone H3K9me3 and H3K27me3 at the promoter of Myc and Ccnd1 genes may be related to the inhibitory effect on oncogene expression in the livers of STL-treated rats.
SCOPE: Emerging evidence indicates that the use of bioactive food components is a promising strategy to prevent the development of liver cancer. The goal of this study was to examine the chemopreventive effect of butyrate-containing structured lipids (STLs) produced by an enzymatic interesterification of tributyrin and flaxseed oil on rathepatocarcinogenesis. METHODS AND RESULTS: Male Wistar rats were subjected to a classic "resistant hepatocyte" model of liver carcinogenesis and treated with STLs, tributyrin or flaxseed oil during the initial phases of hepatocarcinogenesis. Treatment with STLs and tributyrin strongly inhibited the development of preneoplastic liver lesions. The chemopreventive activity of tributyrin was associated with the induction of apoptosis and reduction of the expression of major activated hepatocarcinogenesis-related oncogenes. Treatment with STLs caused substantially greater inhibitory effects than tributyrin on oncogene expression. CONCLUSION: These results demonstrate that the tumor-suppressing activity of butyrate-containing STLs is associated with its ability to prevent and inhibit activation of major hepatocarcinogenesis-related oncogenes. Enrichment of histone H3K9me3 and H3K27me3 at the promoter of Myc and Ccnd1 genes may be related to the inhibitory effect on oncogene expression in the livers of STL-treated rats.
Authors: Aline de Conti; Volodymyr Tryndyak; Renato Heidor; Leandro Jimenez; Fernando Salvador Moreno; Frederick A Beland; Ivan Rusyn; Igor P Pogribny Journal: J Nutr Biochem Date: 2020-09-11 Impact factor: 6.048