Cyclophosphamide and epirubicin induce high apoptosis in microglia cells while epirubicin provokes DNA damage and microglial activation at sub-lethal concentrations.

Autor: de la Hoz-Camacho R; Universidad Autónoma de Nuevo León, Facultad de Ciencias Biológicas, Laboratorio de Inmunología y Virología, Monterrey 66455, Mexico., Rivera-Lazarín AL; Universidad Autónoma de Nuevo León, Facultad de Ciencias Biológicas, Laboratorio de Inmunología y Virología, Monterrey 66455, Mexico., Vázquez-Guillen JM; Universidad Autónoma de Nuevo León, Facultad de Ciencias Biológicas, Laboratorio de Inmunología y Virología, Monterrey 66455, Mexico., Caballero-Hernández D; Universidad Autónoma de Nuevo León, Facultad de Ciencias Biológicas, Laboratorio de Inmunología y Virología, Monterrey 66455, Mexico., Mendoza-Gamboa E; Universidad Autónoma de Nuevo León, Facultad de Ciencias Biológicas, Laboratorio de Inmunología y Virología, Monterrey 66455, Mexico., Martínez-Torres AC; Universidad Autónoma de Nuevo León, Facultad de Ciencias Biológicas, Laboratorio de Inmunología y Virología, Monterrey 66455, Mexico., Rodríguez-Padilla C; Universidad Autónoma de Nuevo León, Facultad de Ciencias Biológicas, Laboratorio de Inmunología y Virología, Monterrey 66455, Mexico.; LONGEVEDEN S.A. de C.V.
Jazyk: angličtina
Zdroj: EXCLI journal [EXCLI J] 2022 Jan 10; Vol. 21, pp. 197-212. Date of Electronic Publication: 2022 Jan 10 (Print Publication: 2022).
DOI: 10.17179/excli2021-4160
Abstrakt: Chemotherapy Related Cognitive Impairment (CRCI), also called chemobrain, diminishes cancer patient's life quality. Breast cancer (BC) patients have been described to be importantly affected, however, the mechanism leading to CRCI has not been fully elucidated. Recent research proposes microglia as the main architect of CRCI, thus dysregulations in these cells could trigger CRCI. The aim of this research was to evaluate the effects of two drugs commonly used against breast cancer, cyclophosphamide (CTX) and epirubicin (EPI), on the microglia cell line SIM-A9, using the BC cell line, 4T1, as a control. Our results show that CTX and EPI decrease microglia-cell viability and increase cell death on a concentration-dependent manner, being 5 and 2 times more cytotoxic to microglia cell line than to breast cancer 4T1cells, respectively. Both chemotherapies induce cell cycle arrest and a significant increase in p53, p16 and γ-H2AX in breast cancer and microglia cells. Furthermore, mitochondrial membrane potential (ΔΨm) diminishes as cell death increases, and both chemotherapies induce reactive oxygen species (ROS) production on SIM-A9 and 4T1. Moreover, caspase activation increases with treatments and its pharmacological blockade inhibits CTX and EPI induced-cell death. Finally, low concentrations of CTX and EPI induce γ-H2AX, and EPI induces cytokine release, NO production and Iba-1 overexpression. These findings indicate that microglia cells are more sensitive to CTX and EPI than BC cells and undergo DNA damage and cell cycle arrest at very low concentrations, moreover EPI induces microglia activation and a pro-inflammatory profile.
(Copyright © 2022 de la Hoz-Camacho et al.)
Databáze: MEDLINE
Externí odkaz: