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G-Quadruplex Binders Induce Immunogenic Cell Death Markers in Aggressive Breast Cancer Cells

Authors :
Nunzia Iaccarino
Bruno Pagano
Jussara Amato
Sarah Di Somma
Anna Maria Malfitano
Giuseppe Portella
Antonio Randazzo
DI SOMMA, Sarah
Amato, Jussara
Iaccarino, Nunzia
Pagano, Bruno
Randazzo, Antonio
Portella, Giuseppe
Malfitano, Anna Maria
Source :
Cancers, Volume 11, Issue 11, Cancers, Vol 11, Iss 11, p 1797 (2019)
Publication Year :
2019

Abstract

Background: DNA G-quadruplex (G4) structures represent potential anti-cancer targets. In this study, we compared the effect of two G4-targeting compounds, C066-3108 and the gold standard BRACO-19. Methods: In breast and prostate cancer cells, cytotoxicity induced by both molecules was measured by a sulforhodamine B assay. In breast cancer cells, cycle, apoptosis, the formation of G4 structures, calreticulin and high mobility group box 1 (HMGB1), as well as T cell activation, were analyzed by flow cytometry and adenosine triphosphate (ATP) by luminescence. Results: Both ligands inhibited cell survival and induced DNA damage. In MCF-7 cells, G4 ligands increased the subG0/G1 phase of the cell cycle inducing apoptosis and reduced intracellular ATP. In untreated MCF-7 cells, we observed a slight presence of G4 structures associated with the G2/M phase. In MDA-MB231 cells, G4 ligands decreased the G1 and enhanced the G2/M phase. We observed a decrease of intracellular ATP, calreticulin cell surface exposure and an increase of HMGB1, accompanied by T cell activation. Both compounds induced G4 structure formation in the subG0/G1 phase. Conclusions: Our data report similar effects for both compounds and the first evidence that G4 ligands induce the release of danger signals associated with immunogenic cell death and induction of T cell activation.

Details

Language :
English
Database :
OpenAIRE
Journal :
Cancers, Volume 11, Issue 11, Cancers, Vol 11, Iss 11, p 1797 (2019)
Accession number :
edsair.doi.dedup.....e3c7a8203d57da261d1412fddb8444ce