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S-Adenosylmethionine Treatment of Colorectal Cancer Cell Lines Alters DNA Methylation, DNA Repair and Tumor Progression-Related Gene Expression
Global DNA hypomethylation is a characteristic feature of colorectal carcinoma (CRC). The tumor inhibitory effect of S-adenosylmethionine (SAM) methyl donor has been described in certain cancers including CRC. However, the molecular impact of SAM treatment on CRC cell lines with distinct genetic fea...
Autores principales: | , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7464653/ https://www.ncbi.nlm.nih.gov/pubmed/32784836 http://dx.doi.org/10.3390/cells9081864 |
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author | Zsigrai, Sára Kalmár, Alexandra Nagy, Zsófia B. Barták, Barbara K. Valcz, Gábor Szigeti, Krisztina A. Galamb, Orsolya Dankó, Titanilla Sebestyén, Anna Barna, Gábor Szabó, Vanessza Pipek, Orsolya Medgyes-Horváth, Anna Csabai, István Tulassay, Zsolt Igaz, Péter Takács, István Molnár, Béla |
author_facet | Zsigrai, Sára Kalmár, Alexandra Nagy, Zsófia B. Barták, Barbara K. Valcz, Gábor Szigeti, Krisztina A. Galamb, Orsolya Dankó, Titanilla Sebestyén, Anna Barna, Gábor Szabó, Vanessza Pipek, Orsolya Medgyes-Horváth, Anna Csabai, István Tulassay, Zsolt Igaz, Péter Takács, István Molnár, Béla |
author_sort | Zsigrai, Sára |
collection | PubMed |
description | Global DNA hypomethylation is a characteristic feature of colorectal carcinoma (CRC). The tumor inhibitory effect of S-adenosylmethionine (SAM) methyl donor has been described in certain cancers including CRC. However, the molecular impact of SAM treatment on CRC cell lines with distinct genetic features has not been evaluated comprehensively. HT-29 and SW480 cells were treated with 0.5 and 1 mmol/L SAM for 48 h followed by cell proliferation measurements, whole-genome transcriptome and methylome analyses, DNA stability assessments and exome sequencing. SAM reduced cell number and increased senescence by causing S phase arrest, besides, multiple EMT-related genes (e.g., TGFB1) were downregulated in both cell lines. Alteration in the global DNA methylation level was not observed, but certain methylation changes in gene promoters were detected. SAM-induced γ-H2AX elevation could be associated with activated DNA repair pathway showing upregulated gene expression (e.g., HUS1). Remarkable genomic stability elevation, namely, decreased micronucleus number and comet tail length was observed only in SW480 after treatment. SAM has the potential to induce senescence, DNA repair, genome stability and to reduce CRC progression. However, the different therapeutic responses of HT-29 and SW480 to SAM emphasize the importance of the molecular characterization of CRC cases prior to methyl donor supplementation. |
format | Online Article Text |
id | pubmed-7464653 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-74646532020-09-04 S-Adenosylmethionine Treatment of Colorectal Cancer Cell Lines Alters DNA Methylation, DNA Repair and Tumor Progression-Related Gene Expression Zsigrai, Sára Kalmár, Alexandra Nagy, Zsófia B. Barták, Barbara K. Valcz, Gábor Szigeti, Krisztina A. Galamb, Orsolya Dankó, Titanilla Sebestyén, Anna Barna, Gábor Szabó, Vanessza Pipek, Orsolya Medgyes-Horváth, Anna Csabai, István Tulassay, Zsolt Igaz, Péter Takács, István Molnár, Béla Cells Article Global DNA hypomethylation is a characteristic feature of colorectal carcinoma (CRC). The tumor inhibitory effect of S-adenosylmethionine (SAM) methyl donor has been described in certain cancers including CRC. However, the molecular impact of SAM treatment on CRC cell lines with distinct genetic features has not been evaluated comprehensively. HT-29 and SW480 cells were treated with 0.5 and 1 mmol/L SAM for 48 h followed by cell proliferation measurements, whole-genome transcriptome and methylome analyses, DNA stability assessments and exome sequencing. SAM reduced cell number and increased senescence by causing S phase arrest, besides, multiple EMT-related genes (e.g., TGFB1) were downregulated in both cell lines. Alteration in the global DNA methylation level was not observed, but certain methylation changes in gene promoters were detected. SAM-induced γ-H2AX elevation could be associated with activated DNA repair pathway showing upregulated gene expression (e.g., HUS1). Remarkable genomic stability elevation, namely, decreased micronucleus number and comet tail length was observed only in SW480 after treatment. SAM has the potential to induce senescence, DNA repair, genome stability and to reduce CRC progression. However, the different therapeutic responses of HT-29 and SW480 to SAM emphasize the importance of the molecular characterization of CRC cases prior to methyl donor supplementation. MDPI 2020-08-09 /pmc/articles/PMC7464653/ /pubmed/32784836 http://dx.doi.org/10.3390/cells9081864 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Zsigrai, Sára Kalmár, Alexandra Nagy, Zsófia B. Barták, Barbara K. Valcz, Gábor Szigeti, Krisztina A. Galamb, Orsolya Dankó, Titanilla Sebestyén, Anna Barna, Gábor Szabó, Vanessza Pipek, Orsolya Medgyes-Horváth, Anna Csabai, István Tulassay, Zsolt Igaz, Péter Takács, István Molnár, Béla S-Adenosylmethionine Treatment of Colorectal Cancer Cell Lines Alters DNA Methylation, DNA Repair and Tumor Progression-Related Gene Expression |
title | S-Adenosylmethionine Treatment of Colorectal Cancer Cell Lines Alters DNA Methylation, DNA Repair and Tumor Progression-Related Gene Expression |
title_full | S-Adenosylmethionine Treatment of Colorectal Cancer Cell Lines Alters DNA Methylation, DNA Repair and Tumor Progression-Related Gene Expression |
title_fullStr | S-Adenosylmethionine Treatment of Colorectal Cancer Cell Lines Alters DNA Methylation, DNA Repair and Tumor Progression-Related Gene Expression |
title_full_unstemmed | S-Adenosylmethionine Treatment of Colorectal Cancer Cell Lines Alters DNA Methylation, DNA Repair and Tumor Progression-Related Gene Expression |
title_short | S-Adenosylmethionine Treatment of Colorectal Cancer Cell Lines Alters DNA Methylation, DNA Repair and Tumor Progression-Related Gene Expression |
title_sort | s-adenosylmethionine treatment of colorectal cancer cell lines alters dna methylation, dna repair and tumor progression-related gene expression |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7464653/ https://www.ncbi.nlm.nih.gov/pubmed/32784836 http://dx.doi.org/10.3390/cells9081864 |
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