Dataset Information

Effect of Sodium Butyrate on LHX1 mRNA Expression as a Transcription Factor of HDAC8 in Human Colorectal Cancer Cell Lines.

ABSTRACT: Background:LHX1 is an important transcription factor for the HDAC8 gene. The aim of this study was to investigate the effect of Sodium Butyrate (SB), as a histone deacetylase inhibitor, on the expression of LHX1 gene in colorectal cancer cell lines. Methods:HT-29 and HCT-116 cell lines were treated with 6.25 to 200 mM concentrations of SB at 24, 48, and 72 hr. The cytotoxicity effect on cell viability was evaluated by MTT assay. The 50% Inhibiting Concentration (IC50) was determined graphically. Quantitative real-time PCR was performed to investigate the LHX1 mRNA expression level. Results:Our study revealed that SB inhibited the proliferation of these cell lines in a concentration and time-dependent manner. The IC50 values for HT-29 cell line were 65, 18.6, and 9.2 mM after 24, 48, and 72 hr of treatment, respectively. The IC50 values for HCT-116 cell line were 35.5, 9.6, and 10 mM after 24, 48, and 72 hr of treatment, respectively. Furthermore, real-time PCR findings demonstrated that the LHX1 mRNA expression in treated HT-29 cell line significantly increased in comparison with untreated cells (p<0.05). However, in treated HCT-116 cell line, SB led to a significant decrease in the level of LHX1 mRNA (p<0.05), as compared to untreated cells. Conclusion:In this study, different effects of SB on LHX1 mRNA expression level were revealed in two distinct human colorectal cancer cell lines.

SUBMITTER: Ghiaghi M

PROVIDER: S-EPMC6925397 | biostudies-literature | 2019 Oct-Dec

REPOSITORIES: biostudies-literature

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Effect of Sodium Butyrate on <i>LHX1</i> mRNA Expression as a Transcription Factor of HDAC8 in Human Colorectal Cancer Cell Lines.

Ghiaghi Mahsa M Forouzesh Flora F Rahimi Hamzeh H

Avicenna journal of medical biotechnology 20191001 4

<h4>Background</h4>LHX1 is an important transcription factor for the <i>HDAC8</i> gene. The aim of this study was to investigate the effect of Sodium Butyrate (SB), as a histone deacetylase inhibitor, on the expression of <i>LHX1</i> gene in colorectal cancer cell lines.<h4>Methods</h4>HT-29 and HCT-116 cell lines were treated with 6.25 to 200 <i>mM</i> concentrations of SB at 24, 48, and 72 <i>hr</i>. The cytotoxicity effect on cell viability was evaluated by MTT assay. The 50% Inhibiting Conce ...[more]

PMID: 31908740

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Project description: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.

Dataset Information

Effect of Sodium Butyrate on LHX1 mRNA Expression as a Transcription Factor of HDAC8 in Human Colorectal Cancer Cell Lines.

Publications

Effect of Sodium Butyrate on <i>LHX1</i> mRNA Expression as a Transcription Factor of HDAC8 in Human Colorectal Cancer Cell Lines.

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