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G-Quadruplex Binders Induce Immunogenic Cell Death Markers in Aggressive Breast Cancer Cells
- 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.
- Subjects :
- 0301 basic medicine
Cancer Research
T cell
Cell
lcsh:RC254-282
Article
Flow cytometry
03 medical and health sciences
0302 clinical medicine
breast cancer
immunogenic cell death markers
medicine
Cytotoxicity
medicine.diagnostic_test
G-quadruplex
Chemistry
T cell activation
Cell cycle
lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens
Molecular biology
030104 developmental biology
medicine.anatomical_structure
Oncology
Apoptosis
030220 oncology & carcinogenesis
Immunogenic cell death
Intracellular
Subjects
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