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Title:
Effects of 5-azacytidine and N6-methyladenosine combination on apoptosis and stemness in human breast cancer stem cells | Molecular Biology Reports
Description:
Background This study investigates the combined effects of the epigenetic anticancer drug 5-azacytidine (5-Aza) and N6-methyladenosine (m6A) on breast cancer stem cells (CSCs) and normal breast epithelial cells. CSCs are characterized by their ability to self-renew, their resistance to conventional therapies, and their role in metastasis, presenting a significant challenge in breast cancer treatment. Methods and results The study utilized flow cytometry to isolate CD44 + /CD24low CSCs from MCF-7 breast cancer cells and evaluated these cells through spheroid formation assays. The results demonstrated that both 5-Aza and m6A, both individually and in combination, exert cytotoxic effects on CSCs, induce apoptosis, and reduce their migratory capacity. Importantly, these treatments did not produce similar effects on normal breast epithelial cells (MCF-10A), indicating selective action on CSCs. Gene expression analysis revealed that treatment with 5-Aza, m6A, and their combination altered the expression of key stem cell-related genes, including OCT4, NANOG, SOX2, and c-MYC, which are associated with CSC self-renewal and malignancy. Conclusions These findings suggest that epigenetic modulation through 5-Aza and m6A could effectively target CSCs, disrupting their ability to drive tumor progression and metastasis, particularly in aggressive breast cancer subtypes. This study highlights the potential of 5-Aza and m6A as a combinatorial therapeutic approach, offering a promising avenue for improving treatment outcomes in breast cancer patients, especially those with therapy-resistant disease. Further clinical investigation is needed to validate these findings and explore their therapeutic implications. Graphical abstract
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Keywords {🔍}
cancer, article, pubmed, cells, stem, google, scholar, breast, cas, central, cell, nmethyladenosine, epigenetic, content, effects, azacytidine, caner, aza, cscs, privacy, cookies, data, biology, combination, stemness, ayse, study, metastasis, access, university, turkey, springer, analysis, information, publish, research, search, discover, methylation, biol, httpsdoiorgs, author, authors, department, ege, izmir, writing, editing, applicable, nature,
Topics {✒️}
month download article/chapter dna methylation insulinoma β-tc-6 cells cbx6-mediated transcriptional repression cancer stem cells cancer stem cells stem cell landscape stem cells access rna n6-methyladenosine modification isolate cd44 + /cd24low cscs breast cancer patients advanced breast cancer full article pdf breast cancer treatment stem cells 32 stem cells 12 spheroid formation assays privacy choices/manage cookies predicts cancer outcome sonic hedgehog signaling targeting epigenetic modifiers article mukhtarova main rna modifications cancer cells breast cancer epithelial-mesenchymal transition related subjects accepted manuscript version therapy-resistant disease promotes cytotoxic autophagy epigenetics exert cytotoxic effects holds exclusive rights ayse caner n6-methyladenosine combination medical biology european economic area indicating selective action produce similar effects modulating epigenetic modifications conditions privacy policy tumor immune microenvironment combination epigenetic therapy personal data cancer therapy combinatorial therapeutic approach cell cycle 12 article log effectively target cscs improving treatment outcomes
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headline:Effects of 5-azacytidine and N6-methyladenosine combination on apoptosis and stemness in human breast cancer stem cells
description:This study investigates the combined effects of the epigenetic anticancer drug 5-azacytidine (5-Aza) and N6-methyladenosine (m6A) on breast cancer stem cells (CSCs) and normal breast epithelial cells. CSCs are characterized by their ability to self-renew, their resistance to conventional therapies, and their role in metastasis, presenting a significant challenge in breast cancer treatment. The study utilized flow cytometry to isolate CD44 + /CD24low CSCs from MCF-7 breast cancer cells and evaluated these cells through spheroid formation assays. The results demonstrated that both 5-Aza and m6A, both individually and in combination, exert cytotoxic effects on CSCs, induce apoptosis, and reduce their migratory capacity. Importantly, these treatments did not produce similar effects on normal breast epithelial cells (MCF-10A), indicating selective action on CSCs. Gene expression analysis revealed that treatment with 5-Aza, m6A, and their combination altered the expression of key stem cell-related genes, including OCT4, NANOG, SOX2, and c-MYC, which are associated with CSC self-renewal and malignancy. These findings suggest that epigenetic modulation through 5-Aza and m6A could effectively target CSCs, disrupting their ability to drive tumor progression and metastasis, particularly in aggressive breast cancer subtypes. This study highlights the potential of 5-Aza and m6A as a combinatorial therapeutic approach, offering a promising avenue for improving treatment outcomes in breast cancer patients, especially those with therapy-resistant disease. Further clinical investigation is needed to validate these findings and explore their therapeutic implications.
datePublished:2025-03-07T00:00:00Z
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description:This study investigates the combined effects of the epigenetic anticancer drug 5-azacytidine (5-Aza) and N6-methyladenosine (m6A) on breast cancer stem cells (CSCs) and normal breast epithelial cells. CSCs are characterized by their ability to self-renew, their resistance to conventional therapies, and their role in metastasis, presenting a significant challenge in breast cancer treatment. The study utilized flow cytometry to isolate CD44 + /CD24low CSCs from MCF-7 breast cancer cells and evaluated these cells through spheroid formation assays. The results demonstrated that both 5-Aza and m6A, both individually and in combination, exert cytotoxic effects on CSCs, induce apoptosis, and reduce their migratory capacity. Importantly, these treatments did not produce similar effects on normal breast epithelial cells (MCF-10A), indicating selective action on CSCs. Gene expression analysis revealed that treatment with 5-Aza, m6A, and their combination altered the expression of key stem cell-related genes, including OCT4, NANOG, SOX2, and c-MYC, which are associated with CSC self-renewal and malignancy. These findings suggest that epigenetic modulation through 5-Aza and m6A could effectively target CSCs, disrupting their ability to drive tumor progression and metastasis, particularly in aggressive breast cancer subtypes. This study highlights the potential of 5-Aza and m6A as a combinatorial therapeutic approach, offering a promising avenue for improving treatment outcomes in breast cancer patients, especially those with therapy-resistant disease. Further clinical investigation is needed to validate these findings and explore their therapeutic implications.
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