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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Butyrate-containing structured lipids act on HDAC4, HDAC6, DNA damage and telomerase activity during promotion of experimental hepatocarcinogenesis

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Festa Ortega, Juliana Festa [1] ; Heidor, Renato [1, 2] ; Auriemo, Ana Paula [1] ; Affonso, Juliana Marques [1] ; D' Amico, Thais Pereira [1] ; Herz, Corinna [3] ; de Conti, Aline [4] ; Ract, Juliana [5] ; Gioieli, Luiz Antonio [5] ; Purgatto, Eduardo [2, 6] ; Lamy, Evelyn [3] ; Pogribny, Igor P. [4] ; Moreno, Fernando Salvador [1, 2]
Total Authors: 13
Affiliation:
[1] Univ Sao Paulo, Fac Pharmaceut Sci, Dept Food & Expt Nutr, Lab Diet Nutr & Canc, Sao Paulo - Brazil
[2] Univ Sao Paulo, Fac Pharmaceut Sci, Food Res Ctr FoRC, Sao Paulo - Brazil
[3] Univ Freiburg, Mol Prevent Med, Breisacherstr 115b, D-79106 Freiburg - Germany
[4] FDA Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR - USA
[5] Univ Sao Paulo, Fac Pharmaceut Sci, Dept Biochem & Pharmaceut Technol, Sao Paulo - Brazil
[6] Univ Sao Paulo, Fac Pharmaceut Sci, Dept Food & Expt Nutr, Lab Food Chem & Biochem, Sao Paulo - Brazil
Total Affiliations: 6
Document type: Journal article
Source: Carcinogenesis; v. 42, n. 8, p. 1026-1036, AUG 2021.
Web of Science Citations: 1
Abstract

Hepatocellular carcinoma (HCC) presents with a high treatment resistance and poor prognosis. Early diagnosis and preventive approaches such as chemoprevention are essential for the HCC control. Therefore, we evaluated the chemopreventive effects of butyrate-containing structured lipids (STLs) administered during the promotion stage of hepatocarcinogenesis in rats submitted to the `resistant hepatocyte' (RH) model. Administration of butyrate-containing STLs inhibited the incidence and mean number of visible hepatic nodules per rat and reduced the number and area of glutathione S-transferase placental form-positive (GST-P+) preneoplastic focal lesions in the livers. This was accompanied by the induction of apoptosis and an increased level of hepatic butyric acid. Treatment with butyrate-containing STLs resulted in increased histone H3 lysine 9 (H3K9) acetylation, reduction of total histone deacetylase (HDAC) activity, and lower levels of HDAC4 and HDAC6 proteins. The chemopreventive effect of butyrate-containing STLs was also associated with the increased nuclear compartmentalization of p53 protein and reduced expression of the Bcl-2 protein. In addition, rats treated with butyrate-containing STLs showed decreased DNA damage and telomerase activity in the livers. These results demonstrate that the suppressive activity of butyrate-containing STLs is associated with inhibition of elevated during hepatocarcinogenesis chromatin-modifying proteins HDAC4 and HDAC6, subcellular redistribution of the p53 protein, and decreased DNA damage and telomerase activity. (AU)

FAPESP's process: 13/07914-8 - FoRC - Food Research Center
Grantee:Bernadette Dora Gombossy de Melo Franco
Support Opportunities: Research Grants - Research, Innovation and Dissemination Centers - RIDC
FAPESP's process: 17/22495-2 - Evaluation of the chemopreventive and anticarcinogeneic potential of structured lipids obtained by interesterification of tributyrin and tricaprylin in experimental hepatocarcinogenesis
Grantee:Fernando Salvador Moreno
Support Opportunities: Regular Research Grants