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Histone modifications play a key role in the epigenetic regulation of gene transcription in cancer cells. Histone acetylations are regulated by two classes of enzymes, histone acetyltransferases (HATs) and histone deacetylases (HDACs). HDACs are increased in ovarian carcinomas and they are involved in carcinogenesis and resistance to chemotherapeutic agents. In our study we investigated anticancer effect of HDAC inhibitor sodium butyrate (NaBu) on cisplatin-sensitive and cisplatin-resistant ovarian cell lines A2780 and A2780cis. A2780 and A2780cis were treated with NaBu alone or in combination with cisplatin (CP). NaBu inhibited the growth of both cell lines and enhanced cytotoxic effect of CP. Exposure to NaBu for 24 h induced cell cycle arrest. The expressions of EMT-related genes and proteins were further investigated by qPCR and western blot analysis. Loss of E-cadherin has been shown to be crucial in ovarian cancer development. We found that NaBu dramatically induce expression of E-cadherin gene (CDH1) and protein levels in A2780 and A2780cis. We investigated correlation between transcription and methylation of CDH1gene. Methylation level analysis in 32 CpG sites in CDH1 gene (promoter/exon1 regions) was performed using bisulfite NGS (Next Generation Sequencing). We found that cisplatin-resistant cell line A2780cis cells differ from their cisplatin-sensitive counterparts in the CDH1 methylation. Methylation in A2780cis cells is elevated compared to A2780. However, NaBu-induced expression of CDH1 was not accompanied by CDH1 demethylation. NaBu treatment induced changes in expression of EMT-related genes and proteins. Interestingly E-cadherin zinc finger transcriptional repressor SNAIL1 was upregulated in both cell lines. Mesenchymal marker vimentin was downregulated. Matrix metalloproteases (MMPs) are necessary for pericellular proteolysis and facilitate migration and invasion of tumour cells. NaBu induced mRNA expression of MMPs, mild changes in activities of gelatinases MMP2 and MMP9 were detected. Our data demonstrate that NaBu sensitizes cisplatin-resistant ovarian cancer cells, re-established E-cadherin expression, but it was not able to reverse the EMT phenotype completely.
This article was published in the following journal.
Name: PloS one
Neuroblastoma (NB) is a type of solid extracranial tumor that usually occurs in babies and children. Chemotherapy is a common method for NB treatment, however, the drug resistance exerts during the ch...
The aim of this study was to determine the effect of exogenous butyrate on the structure and selected functions of the stomach in sheep. Eighteen rams (30.8 ± 2.1 kg; 12 to 15 mo of age) were allocat...
The aim of this study was to determine the effect of exogenous butyrate on the activity of carbohydrate-digesting enzymes in the reticuloruminal digesta and structure and selected functions of the sma...
A shared feature of herpesviruses is their ability to enter a latent state following an initially lytic infection. Marek's disease virus serotype 1 (MDV-1) is an oncogenic avian herpesvirus. Small RNA...
The objective of this study was to determine the effect of varying levels of sodium butyrate (SB) supplementation in feed on the growth, digestibility, and health of postweaned heifers. Forty Holstein...
The purpose of this grant is to evaluate the efficacy of sodium butyrate as a novel treatment for cognitive deficits in schizophrenia (SZ). The proposal consists of a small preliminary op...
The purpose of this grant is to evaluate the efficacy of sodium butyrate as a novel treatment for cognitive deficits in schizophrenia (SZ). The aims will be to evaluate its effects on impr...
In this placebo-controlled randomized parallel study the effects of a butyrate enema on plasma short-chain fatty acids (SCFA) concentrations and fluxes from portal drained viscera, liver a...
Short chain fatty acids (mainly acetate, propionate and butyrate) are produced in the large intestine by bacterial fermentation of unabsorbed carbohydrates, such as dietary fibers. Mainly ...
Shigellosis is one of the major causes of morbidity and mortality in many developing countries. The continued emergence of antibiotic resistant strains has complicated the treatment of shi...
An inorganic and water-soluble platinum complex. After undergoing hydrolysis, it reacts with DNA to produce both intra and interstrand crosslinks. These crosslinks appear to impair replication and transcription of DNA. The cytotoxicity of cisplatin correlates with cellular arrest in the G2 phase of the cell cycle.
Proteins whose abnormal expression (gain or loss) are associated with the development, growth, or progression of NEOPLASMS. Some neoplasm proteins are tumor antigens (ANTIGENS, NEOPLASM), i.e. they induce an immune reaction to their tumor. Many neoplasm proteins have been characterized and are used as tumor markers (TUMOR MARKERS, BIOLOGICAL) when they are detectable in cells and body fluids as monitors for the presence or growth of tumors. Abnormal expression of ONCOGENE PROTEINS is involved in neoplastic transformation, whereas the loss of expression of TUMOR SUPPRESSOR PROTEINS is involved with the loss of growth control and progression of the neoplasm.
Voltage-gated sodium channel subunits that play a role in the assembly, expression, and functional modulation of the sodium channel. They form a heterotrimeric complex with the pore-forming sodium channel alpha subunits.
The study of the relationship between NUTRITIONAL PHYSIOLOGY and genetic makeup. It includes the effect of different food components on GENE EXPRESSION and how variations in GENES effect responses to food components.
Sodium or sodium compounds used in foods or as a food. The most frequently used compounds are sodium chloride or sodium glutamate.
Within medicine, nutrition (the study of food and the effect of its components on the body) has many different roles. Appropriate nutrition can help prevent certain diseases, or treat others. In critically ill patients, artificial feeding by tubes need t...
The development and maintenance of an organism is orchestrated by a set of chemical reactions that switch parts of the genome off and on at strategic times and locations. Epigenetics is the study of these reactions and the factors that influence them. ...