Butyrate-containing structured lipids act on HDAC4, HDAC6, DNA damage and telomerase activity during promotion of experimental hepatocarcinogenesis. (17th May 2021)

• Record Type: Journal Article
• Authors: Ortega, Juliana Festa; Heidor, Renato; Auriemo, Ana Paula; Marques Affonso, Juliana; Pereira D' Amico, Thais; Herz, Corinna; de Conti, Aline; Ract, Juliana; Gioieli, Luiz Antônio; Purgatto, Eduardo; Lamy, Evelyn; P. Pogribny, Igor; Salvador Moreno, Fernando
• Is Part Of: Carcinogenesis. Volume 42:Number 8(2021)
• Page Start: 1026
• Page End: 1036
• Publication Date: 2021-05-17
• Subjects: Carcinogenesis -- Periodicals; Cancer -- Genetic aspects -- Periodicals; Cancer -- Prevention -- Periodicals; Cancer -- Periodicals; 616.994071
• DOI: 10.1093/carcin/bgab039
• Languages: English
• ISSNs: 0143-3334

Abstract

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. Abstract : The chemopreventive effects of butyrate-containing structured lipids during the promotion stage of hepatocarcinogenesis in rats are associated with the inhibition of chromatin-modifying proteins HDAC4 and HDAC6 elevated during hepatocarcinogenesis, subcellular redistribution of the p53 protein, and decreased DNA damage and telomerase activity.