Cargando…
Structural and Biological Features of G-Quadruplex Aptamers as Promising Inhibitors of the STAT3 Signaling Pathway
In this paper, we investigate the structural and biological features of G-quadruplex (G4) aptamers as promising antiproliferative compounds affecting the STAT3 signalling pathway. Targeting the STAT3 protein through high-affinity ligands to reduce its levels or activity in cancer has noteworthy ther...
Autores principales: | , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2023
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10253491/ https://www.ncbi.nlm.nih.gov/pubmed/37298475 http://dx.doi.org/10.3390/ijms24119524 |
_version_ | 1785056418565455872 |
---|---|
author | Esposito, Veronica Benigno, Daniela Bello, Ivana Panza, Elisabetta Bucci, Mariarosaria Virgilio, Antonella Galeone, Aldo |
author_facet | Esposito, Veronica Benigno, Daniela Bello, Ivana Panza, Elisabetta Bucci, Mariarosaria Virgilio, Antonella Galeone, Aldo |
author_sort | Esposito, Veronica |
collection | PubMed |
description | In this paper, we investigate the structural and biological features of G-quadruplex (G4) aptamers as promising antiproliferative compounds affecting the STAT3 signalling pathway. Targeting the STAT3 protein through high-affinity ligands to reduce its levels or activity in cancer has noteworthy therapeutic potential. T40214 (STAT) [(G(3)C)(4)] is a G4 aptamer that can influence STAT3 biological outcomes in an efficient manner in several cancer cells. To explore the effects of an extra cytidine in second position and/or of single site-specific replacements of loop residues in generating aptamers that can affect the STAT3 biochemical pathway, a series of STAT and STATB [GCG(2)(CG(3))(3)C] analogues containing a thymidine residue instead of cytidines was prepared. NMR, CD, UV, and PAGE data suggested that all derivatives adopt dimeric G4 structures like that of unmodified T40214 endowed with higher thermal stability, keeping the resistance in biological environments substantially unchanged, as shown by the nuclease stability assay. The antiproliferative activity of these ODNs was tested on both human prostate (DU145) and breast (MDA-MB-231) cancer cells. All derivatives showed similar antiproliferative activities on both cell lines, revealing a marked inhibition of proliferation, particularly at 72 h at 30 µM. Transcriptomic analysis aimed to evaluate STAT’s and STATB’s influence on the expression of many genes in MDA-MB-231 cells, suggested their potential involvement in STAT3 pathway modulation, and thus their interference in different biological processes. These data provide new tools to affect an interesting biochemical pathway and to develop novel anticancer and anti-inflammatory drugs. |
format | Online Article Text |
id | pubmed-10253491 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-102534912023-06-10 Structural and Biological Features of G-Quadruplex Aptamers as Promising Inhibitors of the STAT3 Signaling Pathway Esposito, Veronica Benigno, Daniela Bello, Ivana Panza, Elisabetta Bucci, Mariarosaria Virgilio, Antonella Galeone, Aldo Int J Mol Sci Article In this paper, we investigate the structural and biological features of G-quadruplex (G4) aptamers as promising antiproliferative compounds affecting the STAT3 signalling pathway. Targeting the STAT3 protein through high-affinity ligands to reduce its levels or activity in cancer has noteworthy therapeutic potential. T40214 (STAT) [(G(3)C)(4)] is a G4 aptamer that can influence STAT3 biological outcomes in an efficient manner in several cancer cells. To explore the effects of an extra cytidine in second position and/or of single site-specific replacements of loop residues in generating aptamers that can affect the STAT3 biochemical pathway, a series of STAT and STATB [GCG(2)(CG(3))(3)C] analogues containing a thymidine residue instead of cytidines was prepared. NMR, CD, UV, and PAGE data suggested that all derivatives adopt dimeric G4 structures like that of unmodified T40214 endowed with higher thermal stability, keeping the resistance in biological environments substantially unchanged, as shown by the nuclease stability assay. The antiproliferative activity of these ODNs was tested on both human prostate (DU145) and breast (MDA-MB-231) cancer cells. All derivatives showed similar antiproliferative activities on both cell lines, revealing a marked inhibition of proliferation, particularly at 72 h at 30 µM. Transcriptomic analysis aimed to evaluate STAT’s and STATB’s influence on the expression of many genes in MDA-MB-231 cells, suggested their potential involvement in STAT3 pathway modulation, and thus their interference in different biological processes. These data provide new tools to affect an interesting biochemical pathway and to develop novel anticancer and anti-inflammatory drugs. MDPI 2023-05-30 /pmc/articles/PMC10253491/ /pubmed/37298475 http://dx.doi.org/10.3390/ijms24119524 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Esposito, Veronica Benigno, Daniela Bello, Ivana Panza, Elisabetta Bucci, Mariarosaria Virgilio, Antonella Galeone, Aldo Structural and Biological Features of G-Quadruplex Aptamers as Promising Inhibitors of the STAT3 Signaling Pathway |
title | Structural and Biological Features of G-Quadruplex Aptamers as Promising Inhibitors of the STAT3 Signaling Pathway |
title_full | Structural and Biological Features of G-Quadruplex Aptamers as Promising Inhibitors of the STAT3 Signaling Pathway |
title_fullStr | Structural and Biological Features of G-Quadruplex Aptamers as Promising Inhibitors of the STAT3 Signaling Pathway |
title_full_unstemmed | Structural and Biological Features of G-Quadruplex Aptamers as Promising Inhibitors of the STAT3 Signaling Pathway |
title_short | Structural and Biological Features of G-Quadruplex Aptamers as Promising Inhibitors of the STAT3 Signaling Pathway |
title_sort | structural and biological features of g-quadruplex aptamers as promising inhibitors of the stat3 signaling pathway |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10253491/ https://www.ncbi.nlm.nih.gov/pubmed/37298475 http://dx.doi.org/10.3390/ijms24119524 |
work_keys_str_mv | AT espositoveronica structuralandbiologicalfeaturesofgquadruplexaptamersaspromisinginhibitorsofthestat3signalingpathway AT benignodaniela structuralandbiologicalfeaturesofgquadruplexaptamersaspromisinginhibitorsofthestat3signalingpathway AT belloivana structuralandbiologicalfeaturesofgquadruplexaptamersaspromisinginhibitorsofthestat3signalingpathway AT panzaelisabetta structuralandbiologicalfeaturesofgquadruplexaptamersaspromisinginhibitorsofthestat3signalingpathway AT buccimariarosaria structuralandbiologicalfeaturesofgquadruplexaptamersaspromisinginhibitorsofthestat3signalingpathway AT virgilioantonella structuralandbiologicalfeaturesofgquadruplexaptamersaspromisinginhibitorsofthestat3signalingpathway AT galeonealdo structuralandbiologicalfeaturesofgquadruplexaptamersaspromisinginhibitorsofthestat3signalingpathway |