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Biomedicine & Pharmacotherapy

Biomedicine & Pharmacotherapy

IF: 6.9
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5-aza-2′-deoxycytidine induces telomere dysfunction in breast cancer cells

Published:26 July 2024 DOI: 10.1016/j.biopha.2024.117173 PMID: 39059352
Sarah Al-dulaimi , Sheila Matta , Predrag Slijepcevic , Terry Roberts

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.

Substances (2)

Related products
Procduct Name CAS Molecular Formula Supplier Price
5-Azacytidine 320-67-2 C8H12N4O5 677 suppliers $7.00-$1767.15
5-Aza-2'-deoxycytidine 2353-33-5 C8H12N4O4 630 suppliers $13.00-$2480.00

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