Effect of valproic acid and zebularine on SOCS-1 and SOCS-3 gene expression in colon carcinoma SW48 cell line

Valproic acid (VPA) and lithium are widely used in the treatment of bipolar disorder. However, the underlying mechanism of action of these drugs is not clearly understood. We used RNA-Seq analysis to examine the global profile of gene expression in a rat serotonergic cell line (RN46A) after exposure to these two mood stabilizer drugs. Numerous genes were differentially regulated in response to VPA (log2 fold change ≥ 1.0; i.e., odds ratio of ≥2, at false discovery rate <5%), but only two genes ( Dynlrb2 and Cdyl2) showed significant differential regulation after exposure of the cells to lithium, with the same analysis criteria. Both of these genes were also regulated by VPA. Many of the differentially expressed genes had functions of potential relevance to mood disorders or their treatment, such as several serpin family genes (including neuroserpin), Nts (neurotensin), Maob (monoamine oxidase B), and Ap2b1, which is important for synaptic vesicle function. Pathway analysis revealed significant enrichment of Gene Ontology terms such as extracellular matrix remodeling, cell adhesion, and chemotaxis. This study in a cell line derived from the raphe nucleus has identified a range of genes and pathways that provide novel insights into potential therapeutic actions of the commonly used mood stabilizer drugs.

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Effects of 5-aza-2ˈ-deoxycytidine and Valproic Acid on Epigenetic-modifying DNMT1 Gene Expression, Apoptosis Induction and Cell Viability in Hepatocellular Carcinoma WCH-17 cell line

Iranian Journal of Pediatric Hematology & Oncology ◽

10.18502/ijpho.v9i2.607 ◽

2019 ◽

Author(s):

Masumeh Sanaei ◽

Fraidoon Kavoosi

Keyword(s):

Gene Expression ◽

Hepatocellular Carcinoma ◽

Valproic Acid ◽

Cell Growth ◽

Cell Line ◽

Dna Methyltransferase ◽

Transcriptional Control ◽

Treatment Time ◽

Induced Apoptosis ◽

Apoptotic Effects

Background: DNA molecule of the eukaryotic cells is found in the form of a nucleoprotein complex named chromatin. Two epigenetic modifications are critical for transcriptional control of genes, including acetylation and DNA methylation. Hypermethylation of tumor suppressor genes is catalyzed by various DNA methyltransferase enzymes (DNMTs), including DNMT1, DNMT2, and DNMT3. The most well characterized DNA demetilating and histone deacetylase inhibitor drugs are 5-aza-2ˈ-deoxycytidine (5-Aza-CdR) and valproic acid (VPA), respectively. The purpose of the current study was to analyze the effects of 5-Aza-CdR and VPA on cell growth, apoptosis, and DNMT1 gene expression in the WCH-17 hepatocellular carcinoma (HCC) cell line. Materials and Methods: In this descriptive analytical study, MTT assay, flow cytometry assay, and Quantitative Real-Time RT-PCRwere done to evaluate proliferative and apoptotic effects and also gene expression. Results: Both compounds inhibited the cell growth and induced apoptosis significantly in a dose and time depended fashion. Additionally, 5-Aza-CdR down-regulated DNMT1 gene expression. The relative expression of DNMT1 was 0.40 and 0.20 (P < 0.001) at different times, respectively. The percentage of VPA- treated apoptotic cells were reduced by about 28 and 34 % (P˂0.001) and that of 5-Aza-CdR-treated were reduced by about 34 and 44 % (P˂0.001) after treatment time periods. Conclusion: In the current study, it was observed that 5-Aza-CdR and VPA could significantly inhibit the growth of WCH-17 cell and played a significant role in apoptosis. It was also found that 5-Aza-CdR could decrease DNMT1 gene expression.

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Gene expression effects of lithium and valproic acid in a serotonergic cell line

10.1101/227652 ◽

2017 ◽

Author(s):

Diana Balasubramanian ◽

John F. Pearson ◽

Martin A. Kennedy

Keyword(s):

Gene Expression ◽

Valproic Acid ◽

Cell Line ◽

Mood Stabilizer ◽

Underlying Mechanism ◽

Rna Seq ◽

Significant Enrichment ◽

A Cell ◽

Global Profile ◽

Serotonergic Cell

AbstractValproic acid (VPA) and lithium are widely used in the treatment of bipolar disorder. However, the underlying mechanism of action of these drugs is not clearly understood. We used RNA-Seq analysis to examine the global profile of gene expression in a rat serotonergic cell line (RN46A) after exposure to these two mood stabilizer drugs. Numerous genes were differentially regulated in response to VPA (log2 fold change ≥ 1.0; i.e. odds ratio of ≥ 2, at FDR <5%), but only two genes (Dynlrb2 and Cdyl2) showed significant differential regulation after exposure of the cells to lithium, with the same analysis criteria. Both of these genes were also regulated by VPA. Many of the differentially expressed genes had functions of potential relevance to mood disorders or their treatment, such as several serpin family genes (including neuroserpin), Nts (neurotensin), Maob (monoamine oxidase B) and Ap2b1, which is important for synaptic vesicle function. Pathway analysis revealed significant enrichment of Gene Ontology terms such as extracellular matrix (ECM) remodelling, cell adhesion and chemotaxis. This study in a cell line derived from the raphe nucleus has identified a range of genes and pathways that provide novel insights into the therapeutic action of the commonly used mood stabilizer drugs.

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