Sequential gene expression changes in cancer cell lines after treatment with the demethylation agent 5‐Aza‐2′‐deoxycytidine

Arai, Makoto; Yokosuka, Osamu; Hirasawa, Yuichi; Fukai, Kenichi; Chiba, Tetsuhiro; Imazeki, Fumio; Yatomi, Mari; Takiguchi, Yuichi; Seki, Naohiko; Saisho, Hiromitsu; Ochiai, Takenori

doi:10.1002/cncr.21905

Cited by 25 publications

(23 citation statements)

References 30 publications

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“…34 Overall, gene expression profiles were similar, but there were differences in the expression of several genes between HepG2 and Huh7 cells. 35 Our findings suggest that the effect of AgNPs on metabolism may vary according to cell type, and thus further study is necessary to determine the effect of AgNPs on metabolism in the different types of cells. In our study, PEPCK mRNA levels were not altered, but Nrf2 level was reduced in hepatoma cells 2 hours after AgNP treatment.…”

Section: Discussionmentioning

confidence: 84%

Silver nanoparticles affect glucose metabolism in hepatoma cells through production of reactive oxygen species

Lee

Lee²,

Yun³

et al. 2015

IJN

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The silver nanoparticle (AgNP) is a candidate for anticancer therapy because of its effects on cell survival and signaling. Although numerous reports are available regarding their effect on cell death, the effect of AgNPs on metabolism is not well understood. In this study, we investigated the effect of AgNPs on glucose metabolism in hepatoma cell lines. Lactate release from both HepG2 and Huh7 cells was reduced with 5 nm AgNPs as early as 1 hour after treatment, when cell death did not occur. Treatment with 5 nm AgNPs decreased glucose consumption in HepG2 cells but not in Huh7 cells. Treatment with 5 nm AgNPs reduced nuclear factor erythroid 2-like 2 expression in both cell types without affecting its activation at the early time points after AgNPs’ treatment. Increased reactive oxygen species (ROS) production was detected 1 hour after 5 nm AgNPs’ treatment, and lactate release was restored in the presence of an ROS scavenger. Our results suggest that 5 nm AgNPs affect glucose metabolism by producing ROS.

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Section: Discussionmentioning

confidence: 84%

Silver nanoparticles affect glucose metabolism in hepatoma cells through production of reactive oxygen species

Lee

Lee²,

Yun³

et al. 2015

IJN

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“…Bisulfite genomic sequencing was used to determine the methylation status of promoter regions. By clustering analysis based on expression patterns, we revealed in our previous report that there were 206 genes upregulated by 5-AzaC in at least one HCC cell line and 80 genes upregulated by 5-AzaC in at least two cell lines [11]. To choose the candidate genes regulated by this epigenetic factor, we performed simple linear regression analysis with the statistical program StatView (SAS, Cary, N.C., USA).…”

Section: Methodsmentioning

confidence: 99%

“…In previous studies, we used the microarray system to define the genes upregulated by 5-AzaC treatment [10] and to define serial changes in gene expression in six hepatoma cell lines induced by transient treatment with 5-AzaC for 24–120 h. Based upon the results of these studies, we selected candidate genes that may be regulated by epigenetic factors [11]. In this study,we assessed the methylation status of CpG islands within the promoters of these twelve genes and examined the status of the aberrantly methylated genes in terms of the difference in methylation between HCC and non-HCC tissues.…”

Section: Introductionmentioning

confidence: 99%

Methylation Status of Genes Upregulated by Demethylating Agent 5-aza-2′-Deoxycytidine in Hepatocellular Carcinoma

Hirasawa¹,

Arai

Imazeki³

et al. 2006

Oncology

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Background/Aims: To determine the clinical significance of gene promoter methylation in hepatocellular carcinoma (HCC), we examined in clinical samples the methylation status of those promoters that showed elevated activity in hepatoma cell lines after 5-aza-2′-deoxycytidine treatment. Methods: Regarding the genes with promoter hypermethylation in the cell lines, their expression levels and methylation status in HCC and non-HCC tissues were assessed by semiquantitive RT-PCR and methylation-specific PCR. To confirm the result, the expression levels and methylation status in 16 additional HCC and non-HCC tissues were assessed. Results: The promoter regions of caveolin 1 (CAV1), cysteine and glycine-rich protein 1 (CSRP1), Kruppel-like factor 6 (KLF6), myosin (light polypeptide 9) (MYL9), and transgelin (TAGLN) were highly methylated in the cell lines. CAV1 and CSRP1 were methylated in HCC more frequently than in non-HCC. KLF6, MYL9, and TAGLN were fully methylated in both HCC and non-HCC. Using additional clinical samples, downregulation of CAV1 and CSRP1 was observed in 38 and 56%, respectively, of the 16 HCC samples and aberrant methylation of CAV1 and CSRP1 was observed in 56% of HCC in both cases. Conclusion:CAV1 and CSRP1 were inactivated in HCC by aberrant methylation and they may serve as important biomarkers of malignancy.

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“…For this purpose, DAC and TSA were used as a DNA methylation inhibitor and a histone deacetylase inhibitor, respectively. 25,26) The mRNA expression of SMCT1, THTR2 and MATE1 was induced by DAC treatment in HCT116 and SW48 cells lacking their expressions. In addition, in HCT116 and SW48 cells, methylated DNA in the promoter region of THTR2, SMCT1 and MATE1 decreased by DAC treatment, while unmethylated DNA increased.…”

Section: Fig 2 Msp Analysis Of the Upstream Region Of Tss In Colon mentioning

confidence: 99%

Different Involvement of DNA Methylation and Histone Deacetylation in the Expression of Solute-Carrier Transporters in 4 Colon Cancer Cell Lines

Ikehata

Iwakawa

2012

Biological & Pharmaceutical Bulletin

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The purpose of this study on the involvement of epigenetic control of the expression of solute carrier (SLC) transporters by DNA methylation and histone deacetylation in 4 colon cancer cells is to find the epigenetic control mechanisms of drug transporters in colon cancers. Human colon cancer cell lines (HCT116, HT29, SW48, SW480) were treated with 5-aza-2′-deoxycytidine (DAC), as a DNA methyltransferase inhibitor, followed by trichostatin A (TSA), as a histone deacetylase inhibitor. The mRNA expression and DNA methylation of several SLC transporters were analyzed by real-time polymerase chain reaction (PCR) and methylation-specific PCR, respectively. Among 12 SLC transporters possessing cytosine-phosphate-guanine (CpG) islands, thiamine transporter 2 (THTR2) (SLC19A3) gene showed a correlation between its mRNA expression level and DNA methylation status. TSA treatment increased histone H3 acetylation of THTR2 promoter region in all 4 colon cancer cell lines examined. HCT116 and SW48 cells showed a lack of THTR2 mRNA expression and methylation of its promoter, and DAC treatment induced its re-expression. In addition, the co-treatment with DAC and TSA increased THTR2 mRNA expression more markedly than DAC treatment in HCT116 and SW48 cells. In HT29 and SW480 cells that showed little methylation of THTR2 promoter, TSA treatment induced THTR2 mRNA expression markedly, but DAC treatment did not. In the 4 colon cancer cells examined, THTR2 mRNA expression is down-regulated by DNA methylation and/or histone deacetylation.Key words solute-carrier transporter; DNA methylation; histone deacetylation; colon cancer; epigenetics; cytosine-phosphate-guanine island Epigenetics refers to heritable changes in gene expression that are not coded in the DNA sequence itself. Epigenetic events include methylation of DNA and modifications to histone proteins. The disruption of epigenetic mechanisms such as DNA methylation and histone acetylation can lead to inappropriate expression or silencing of genes, resulting in several major diseases including cancer. In tumors in particular, DNA hypermethylation in cytosine-phosphate-guanine (CpG) islands in the promoter region of a specific gene is often observed. This phenomenon leads to transcriptional downregulation of cancer-related genes like tumor suppressor genes.

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Sequential gene expression changes in cancer cell lines after treatment with the demethylation agent 5‐Aza‐2′‐deoxycytidine

Cited by 25 publications

References 30 publications

Silver nanoparticles affect glucose metabolism in hepatoma cells through production of reactive oxygen species

Silver nanoparticles affect glucose metabolism in hepatoma cells through production of reactive oxygen species

Methylation Status of Genes Upregulated by Demethylating Agent 5-aza-2′-Deoxycytidine in Hepatocellular Carcinoma

Different Involvement of DNA Methylation and Histone Deacetylation in the Expression of Solute-Carrier Transporters in 4 Colon Cancer Cell Lines

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