Circular and linear : a tale of aptamer selection for the activation of SIRT1 to induce death in cancer cells

Al-Sudani, B, Ragazzon-Smith, AH, Aziz, A ORCID: https://orcid.org/0000-0002-8774-0348, Alansari, R, Ferry, N ORCID: https://orcid.org/0000-0003-3728-4302, Krstic- Demonacos, M ORCID: https://orcid.org/0000-0002-3914-4488 and Ragazzon, PA 2020, 'Circular and linear : a tale of aptamer selection for the activation of SIRT1 to induce death in cancer cells' , RSC Advances, 10 (73) , pp. 45008-45018.

[img]
Preview
PDF - Published Version
Available under License Creative Commons Attribution Non-commercial.

Download (1MB) | Preview

Abstract

It is a challenge to select the right target to treat conditions without affecting non-diseased cells. Cancer belongs to the top 10 causes of death in the world and it remains difficult to treat. Amongst cancer emerging targets, silent information regulator 1 (SIRT1) – a histone deacetylase – has shown many roles in cancer, ageing and metabolism. Here we report novel SIRT1 ligands that bind and modulate the activity of SIRT1 within cells and enhance its enzymatic activity. We developed a modified aptamer capable of binding to and forming a complex with SIRT1. Our ligands are aptamers, they can be made of DNA or RNA oligonucleotides, their binding domain can recognise a target with very high affinity and specificity. We used the systematic evolution of ligands by exponential enrichment (SELEX) technique to develop circular and linear aptamers selectively binding to SIRT1. Cellular consequences of the interaction were monitored by fluorescence microscopy, cell viability assay, stability and enzymatic assays. Our results indicate that from our pool of aptamers, circular AC3 penetrates cancerous cells and is recruited to modulate the SIRT1 activity. This modulation of SIRT1 resulted in anticancer activity on different cancer cell lines. Furthermore, this modified aptamer showed no toxicity on one non-cancerous cell line and was stable in human plasma. We have demonstrated that aptamers are efficient tools for localisation of internal cell targets, and in this particular case, anticancer activity through modulation of SIRT1.

Item Type: Article
Schools: Schools > School of Environment and Life Sciences > Biomedical Research Centre
Journal or Publication Title: RSC Advances
Publisher: Royal Society of Chemistry
ISSN: 2046-2069
Related URLs:
Funders: Iraqi Ministry of Higher Education and Scientific Research (MOHESR)
Depositing User: M Krstic- Demonacos
Date Deposited: 04 Jan 2021 11:22
Last Modified: 28 Aug 2021 11:18
URI: http://usir.salford.ac.uk/id/eprint/59220

Actions (login required)

Edit record (repository staff only) Edit record (repository staff only)

Downloads

Downloads per month over past year