Please use this identifier to cite or link to this item:
https://hdl.handle.net/10316/84851
Title: | Single nanomolar doxorubicin exposure triggers compensatory mitochondrial responses in H9c2 cardiomyoblasts | Authors: | Ferreira, Luciana L. Cunha-Oliveira, Teresa Veloso, Caroline D. Costa, Cláudio F. Wallace, Kendall B. Oliveira, Paulo J. |
Issue Date: | Feb-2019 | Serial title, monograph or event: | Food and Chemical Toxicology | Volume: | 124 | Abstract: | Dose-dependent and cumulative cardiotoxicity associated with doxorubicin (DOX) is the main limitation of anticancer therapy. Pediatric cancer survivors are particularly vulnerable, and no effective prevention measures are available. The aim of the present study was to investigate the persistent effects of nanomolar DOX concentrations and determine whether a pretreatment would induce mitochondrial adaptations in H9c2 cardiomyoblasts. H9c2 cells were incubated with DOX (10 and 25 nM) for 24 h, followed by 9 days of recovery in drug-free medium. We found that the sub-therapeutic DOX treatment induced persistent hypertrophy and dose-dependent cell cycle arrest in G2/M. Glycolytic activity, indirectly based on extracellular acidification rate, and basal respiration were significantly decreased in DOX-treated cells compared to controls, although both groups showed similar maximal respiration. Additionally, nanomolar DOX pretreatment resulted in upregulation of mitochondrial DNA transcripts accompanied by a decrease in DNA methyltransferase 1 (DNMT1) and global methylation levels. Finally, the pretreatment with DOX ameliorated H9c2 cells resistance against a subsequent exposure to DOX. These results suggest that nanomolar DOX pretreatment induced a beneficial and possibly epigenetic-based mitochondrial adaptation, raising the possibility that an early sub-therapeutic DOX treatment can be used as a preconditioning and protective approach during anticancer therapies. | URI: | https://hdl.handle.net/10316/84851 | ISSN: | 1873-6351 | DOI: | 10.1016/j.fct.2018.12.017 | Rights: | embargoedAccess |
Appears in Collections: | I&D CNC - Artigos em Revistas Internacionais |
Files in This Item:
File | Description | Size | Format | |
---|---|---|---|---|
35_Ferreiraetal2019_FCT.pdf | 2.2 MB | Adobe PDF | View/Open |
SCOPUSTM
Citations
19
checked on Aug 26, 2024
WEB OF SCIENCETM
Citations
10
18
checked on Aug 2, 2024
Page view(s)
221
checked on Aug 27, 2024
Download(s)
552
checked on Aug 27, 2024
Google ScholarTM
Check
Altmetric
Altmetric
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.