Vitamin D3 attenuates doxorubicin-induced senescence of human aortic endothelial cells by upregulation of IL-10 via the pAMPKα/Sirt1/Foxo3a signaling pathway.
Lei ChenRachel HolderCharles PorterZubair ShahPublished in: PloS one (2021)
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.
Keyphrases
- endothelial cells
- high glucose
- signaling pathway
- pi k akt
- oxidative stress
- diabetic rats
- poor prognosis
- drug delivery
- cell cycle arrest
- cancer therapy
- transcription factor
- drug induced
- vascular endothelial growth factor
- dna damage
- aortic valve
- heart failure
- cell proliferation
- physical activity
- radiation therapy
- pluripotent stem cells
- stress induced
- locally advanced