Vitamin D3 attenuates doxorubicin-induced senescence of human aortic endothelial cells by upregulation of IL-10 via the pAMPKα/Sirt1/Foxo3a signaling pathway

The toxicity of doxorubicin to the cardiovascular system often limits its benefits and widespread use as chemotherapy. The mechanisms involved in doxorubicin-induced cardiovascular damage and possible protective interventions are not well-explored. Using human aortic endothelial cells, we show vitam...

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Bibliographic Details
Published in:PloS one 2021-06, Vol.16 (6), p.e0252816-e0252816
Main Authors: Chen, Lei, Holder, Rachel, Porter, Charles, Shah, Zubair
Format: Article
Language:English
Subjects:
Animal models
Antibodies
Aorta
Biology and Life Sciences
Blood vessels
Cancer
Cardiomyocytes
Cardiomyopathy
Cardiotoxicity
Cell culture
Cell cycle
Cell growth
Culture media
Damage
Doxorubicin
Endothelial cells
Endothelium
Flow cytometry
FOXO3 protein
Gene expression
Inflammation
Interleukin 10
Laboratories
Medicine
Medicine and Health Sciences
Oxidative stress
Paracrine signalling
Prevention
Proteins
Reagents
Research and Analysis Methods
Senescence
Signal transduction
SIRT1 protein
Toxicity
Up-regulation
Vitamin D3
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Summary:The toxicity of doxorubicin to the cardiovascular system often limits its benefits and widespread use as chemotherapy. The mechanisms involved in doxorubicin-induced cardiovascular damage and possible protective interventions are not well-explored. Using human aortic endothelial cells, we show vitamin D3 strongly attenuates doxorubicin-induced senescence and cell cycle arrest. We further show the protective effects of vitamin D3 are mediated by the upregulation of IL-10 and FOXO3a expression through fine modulation of pAMPKα/SIRT1/FOXO3a complex activity. These results have great significance in finding a target for mitigating doxorubicin-induced cardiovascular toxicity.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0252816