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Evaluation of the chemopreventive and anticarcinogeneic potential of structured lipids obtained by interesterification of tributyrin and tricaprylin in experimental hepatocarcinogenesis

Grant number: 17/22495-2
Support type:Regular Research Grants
Duration: August 01, 2018 - January 31, 2022
Field of knowledge:Health Sciences - Nutrition - Nutrition Biochemistry
Principal researcher:Fernando Salvador Moreno
Grantee:Fernando Salvador Moreno
Home Institution: Faculdade de Ciências Farmacêuticas (FCF). Universidade de São Paulo (USP). São Paulo , SP, Brazil
Assoc. researchers: Jens U. Marquardt ; Juliana Neves Rodrigues Ract ; Luiz Antonio Gioielli

Abstract

The combination of chemopreventive agents acting through different mechanisms of action has been considered a promissory strategy for cancer prevention. The butyrate pro-drug tributyrin (TB), which is present in milk fat and honey, has been highlighted for its chemopreventive activity during the initiation and promotion phases of experimental models of hepatocarcinogenesis. TB's inhibitory effects have been attributed to its canonical mechanisms of action, i.e. apoptotic induction, and histone acetylation. It has also been associated with inhibition of angiogenesis in early phases of hepatocarcinogenesis. As TB, tricaprylin (TC) exerted chemopreventive activity in vitro, which seemed to happen through the modulation of tight junctions and the subsequent alteration in paracellular permeability. With the current advances in biotechnology, it is possible to modify the structure of biomolecules in such a way that they can promote the physiological maintenance and the prevention of carcinogenesis. Previously, we demonstrated the carcinogenic inhibitory potential of structured lipids (EST) obtained from the enzymatic interesterification of TB and linseed oil, during the initiation and promotion stages of experimental carcinogenesis. In this regard, the synthesis of new ESTs from long- and medium chain fatty acids bound to a single glycerol molecule after the interesterification of TB and TC emerged as a promissory approach for cancer chemoprevention. Thus, it is now intended to evaluate the chemopreventive activity of EST derived from enzymatic interesterification of TB and TC in different phases of hepatocarcinogenesis. For that purpose, Fischer F-344 rats will be subjected to the Resistant Hepatocyte (RH) model, in which the chemopreventive potential of such ESTs will be assayed by the continuous administration during initiation and promotion phases of the hepatocarcinogenesis. Furthermore, we will test the EST activity in cancer progression using GP7TB, JM-1, and Huh7 cell lines culture. The expression of genes associated with tight junctions and angiogenesis will be screened as a possible target of the eventual chemopreventive action of the new EST. (AU)

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Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
FESTA ORTEGA, JULIANA FESTA; HEIDOR, RENATO; AURIEMO, ANA PAULA; AFFONSO, JULIANA MARQUES; D' AMICO, THAIS PEREIRA; HERZ, CORINNA; DE CONTI, ALINE; RACT, JULIANA; GIOIELI, LUIZ ANTONIO; PURGATTO, EDUARDO; LAMY, EVELYN; POGRIBNY, IGOR P.; MORENO, FERNANDO SALVADOR. Butyrate-containing structured lipids act on HDAC4, HDAC6, DNA damage and telomerase activity during promotion of experimental hepatocarcinogenesis. Carcinogenesis, v. 42, n. 8, p. 1026-1036, AUG 2021. Web of Science Citations: 1.

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