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

Autor(es):Mostrar menos -

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]}

Afiliação do(s) autor(es)

^[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

• Tipo de documento: Artigo Científico
• Fonte: Carcinogenesis; v. 42, n. 8, p. 1026-1036, AUG 2021.
• Citações Web of Science: 1

Resumo

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)

• Processo FAPESP: 13/07914-8 - FoRC - Centro de Pesquisa em Alimentos
• Beneficiário: Bernadette Dora Gombossy de Melo Franco
• Modalidade de apoio: Auxílio à Pesquisa - Centros de Pesquisa, Inovação e Difusão - CEPIDs
• Processo FAPESP: 17/22495-2 - Avaliação do potencial quimiopreventivo e anticarcinogênico de lipídos estruturados obtidos por interesterificação da tributirina com tricaprilina na hepatocarcinogênese experimental
• Beneficiário: Fernando Salvador Moreno
• Modalidade de apoio: Auxílio à Pesquisa - Regular