Butyrate-containing structured lipids act on HDAC4, HDAC6, DNA damage and telomerase activity during promotion of experimental hepatocarcinogenesis.
Carcinogenesis
; 42(8): 1026-1036, 2021 08 19.
Article
em En
| MEDLINE
| ID: mdl-33999989
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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Dano ao DNA
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Butiratos
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Telomerase
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Glutationa S-Transferase pi
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Desacetilase 6 de Histona
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Histona Desacetilases
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Lipídeos
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Neoplasias Hepáticas Experimentais
Tipo de estudo:
Screening_studies
Limite:
Animals
Idioma:
En
Revista:
Carcinogenesis
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
Brasil