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Genome-wide differential DNA methylation analysis of MDA-MB-231 breast cancer cells treated with curcumin derivatives, ST08 and ST09

ST08 and ST09 are potent curcumin derivatives with antiproliferative, apoptotic, and migrastatic properties. Both ST08 and ST09 exhibit in vitro and in vivo anticancer properties. As reported earlier, these derivatives were highly cytotoxic towards MDA-MB-231 triple-negative breast cancer cells with...

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Autores principales: Nirgude, Snehal, Desai, Sagar, Choudhary, Bibha
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9727864/
https://www.ncbi.nlm.nih.gov/pubmed/36474139
http://dx.doi.org/10.1186/s12864-022-09041-2
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author Nirgude, Snehal
Desai, Sagar
Choudhary, Bibha
author_facet Nirgude, Snehal
Desai, Sagar
Choudhary, Bibha
author_sort Nirgude, Snehal
collection PubMed
description ST08 and ST09 are potent curcumin derivatives with antiproliferative, apoptotic, and migrastatic properties. Both ST08 and ST09 exhibit in vitro and in vivo anticancer properties. As reported earlier, these derivatives were highly cytotoxic towards MDA-MB-231 triple-negative breast cancer cells with IC50 values in the nanomolar (40-80nM) range.In this study,we performed whole-genome bisulfite sequencing(WGBS) of untreated (control), ST08 and ST09 (treated) triple-negative breast cancer cell line MDA-MB-231 to unravel epigenetic changes induced by the drug. We identified differentially methylated sites (DMSs) enriched in promoter regions across the genome. Analysis of the CpG island promoter methylation identified 12 genes common to both drugs, and 50% of them are known to be methylated in patient samples that were hypomethylated by drugs belonging to the homeobox family transcription factors.Methylation analysis of the gene body revealed 910 and 952 genes to be hypermethylatedin ST08 and ST09 treated MDA-MB-231 cells respectively. Correlation of the gene body hypermethylation with expression revealed CACNAH1 to be upregulated in ST08 treatment and CDH23 upregulation in ST09.Further, integrated analysis of the WGBS with RNA-seq identified uniquely altered pathways - ST08 altered ECM pathway, and ST09 cell cycle, indicating drug-specific signatures. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12864-022-09041-2.
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spelling pubmed-97278642022-12-08 Genome-wide differential DNA methylation analysis of MDA-MB-231 breast cancer cells treated with curcumin derivatives, ST08 and ST09 Nirgude, Snehal Desai, Sagar Choudhary, Bibha BMC Genomics Research ST08 and ST09 are potent curcumin derivatives with antiproliferative, apoptotic, and migrastatic properties. Both ST08 and ST09 exhibit in vitro and in vivo anticancer properties. As reported earlier, these derivatives were highly cytotoxic towards MDA-MB-231 triple-negative breast cancer cells with IC50 values in the nanomolar (40-80nM) range.In this study,we performed whole-genome bisulfite sequencing(WGBS) of untreated (control), ST08 and ST09 (treated) triple-negative breast cancer cell line MDA-MB-231 to unravel epigenetic changes induced by the drug. We identified differentially methylated sites (DMSs) enriched in promoter regions across the genome. Analysis of the CpG island promoter methylation identified 12 genes common to both drugs, and 50% of them are known to be methylated in patient samples that were hypomethylated by drugs belonging to the homeobox family transcription factors.Methylation analysis of the gene body revealed 910 and 952 genes to be hypermethylatedin ST08 and ST09 treated MDA-MB-231 cells respectively. Correlation of the gene body hypermethylation with expression revealed CACNAH1 to be upregulated in ST08 treatment and CDH23 upregulation in ST09.Further, integrated analysis of the WGBS with RNA-seq identified uniquely altered pathways - ST08 altered ECM pathway, and ST09 cell cycle, indicating drug-specific signatures. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12864-022-09041-2. BioMed Central 2022-12-06 /pmc/articles/PMC9727864/ /pubmed/36474139 http://dx.doi.org/10.1186/s12864-022-09041-2 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Nirgude, Snehal
Desai, Sagar
Choudhary, Bibha
Genome-wide differential DNA methylation analysis of MDA-MB-231 breast cancer cells treated with curcumin derivatives, ST08 and ST09
title Genome-wide differential DNA methylation analysis of MDA-MB-231 breast cancer cells treated with curcumin derivatives, ST08 and ST09
title_full Genome-wide differential DNA methylation analysis of MDA-MB-231 breast cancer cells treated with curcumin derivatives, ST08 and ST09
title_fullStr Genome-wide differential DNA methylation analysis of MDA-MB-231 breast cancer cells treated with curcumin derivatives, ST08 and ST09
title_full_unstemmed Genome-wide differential DNA methylation analysis of MDA-MB-231 breast cancer cells treated with curcumin derivatives, ST08 and ST09
title_short Genome-wide differential DNA methylation analysis of MDA-MB-231 breast cancer cells treated with curcumin derivatives, ST08 and ST09
title_sort genome-wide differential dna methylation analysis of mda-mb-231 breast cancer cells treated with curcumin derivatives, st08 and st09
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9727864/
https://www.ncbi.nlm.nih.gov/pubmed/36474139
http://dx.doi.org/10.1186/s12864-022-09041-2
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