Single nanomolar doxorubicin exposure triggers compensatory mitochondrial responses in H9c2 cardiomyoblasts.
Food Chem Toxicol
; 124: 450-461, 2019 Feb.
Article
en En
| MEDLINE
| ID: mdl-30557669
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 25â¯nM) for 24â¯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.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Doxorrubicina
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Mioblastos Cardíacos
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Mitocondrias Cardíacas
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Antibióticos Antineoplásicos
Límite:
Animals
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Humans
Idioma:
En
Revista:
Food Chem Toxicol
Año:
2019
Tipo del documento:
Article