Vitamin D3 attenuates doxorubicin-induced senescence of human aortic endothelial cells by upregulation of IL-10 via the pAMPKα/Sirt1/Foxo3a signaling pathway
Lei Chen, Rachel Holder, Charles Porter, Zubair Shah
Abstract
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.
Topics & Concepts
Downregulation and upregulationDoxorubicinSenescenceCancer researchVitamin D and neurologyMedicineSirtuin 1PharmacologyEndocrinologyInternal medicineBiologyChemotherapyBiochemistryGeneChemotherapy-induced cardiotoxicity and mitigationAntioxidant Activity and Oxidative StressAtherosclerosis and Cardiovascular Diseases