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Title: | 5-aza-2′-deoxycytidine induces telomere dysfunction in breast cancer cells |
Authors: | Al-dulaimi, S Matta, S Slijepcevic, P Roberts, T |
Keywords: | telomere;telomerase;ALT;breast cancer |
Issue Date: | 26-Jul-2024 |
Publisher: | Elsevier Masson SAS |
Citation: | Al-dulaimi, S. et al. (2024) ‘5-aza-2′-deoxycytidine induces telomere dysfunction in breast cancer cells’, Biomedicine and Pharmacotherapy, 178, 117173, pp. 1 - 10. doi:https://doi.org/10.1016/j.biopha.2024.117173. |
Abstract: | Aims: Azacitidine, a drug that epigenetically modifies DNA, is widely used to treat haematological malignancies. However, at low doses, it demethylates DNA, and as a result, can alter gene expression. In our previous publication, we showed that low doses of azacitidine induce telomere length elongation in breast cancer cells. In this study, we aim to identify the mechanisms which lead to telomere length increases. Methods: Breast cancer cell lines representing different molecular sub-types were exposed to 5-aza-2′-deoxycytidine (5-aza) in 2 and 3D cultures, followed by DNA, RNA, and protein extractions. Samples were then analysed for telomere length, DNA damage, telomerase, and ALT activity. Results: We show that treatment of the cell lines with 5-aza for 72 h induced DNA damage at the telomeres and increased ALT activity 3-fold. We also identified a gene, POLD3, which may be involved in the ALT activity seen after treatment. Conclusion: Our results indicate that while 5-aza is a useful drug for treating haematological cancers, surviving cancer cells that have been exposed to lower doses of the drug may activate mechanisms such as ALT. This could lead to cancer cell survival and possible resistance to 5-aza clinically. |
Description: | Supplementary material is available online at: https://www.sciencedirect.com/science/article/pii/S0753332224010576?via%3Dihub#sec0140 . |
URI: | https://bura.brunel.ac.uk/handle/2438/29475 |
DOI: | https://doi.org/10.1016/j.biopha.2024.117173 |
ISSN: | 0753-3322 |
Other Identifiers: | ORCiD: Predrag Slijepcevic https://orcid.org/0000-0003-0168-3598 ORCiD: Terry Roberts https://orcid.org/0000-0002-6738-2176 117173 |
Appears in Collections: | Dept of Life Sciences Research Papers |
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