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

• DOI: 10.1371/journal.pone.0252816
• Publication Date: 2021-06-08T18:26:40Z
• Authors: Lei Chen; Rachel Holder; Charles Porter; Zubair Shah
• Keywords: 0301 basic medicine; Science; Primary Cell Culture; Gene Expression; AMP-Activated Protein Kinases; 03 medical and health sciences; Sirtuin 1; Humans; Aorta; Cells, Cultured; Cellular Senescence; Cholecalciferol; Antibiotics, Antineoplastic; Q; Forkhead Box Protein O3; R; Endothelial Cells; Proteins; Vitamins; Interleukin-10; Up-Regulation; 3. Good health; Doxorubicin; Medicine; Research Article; Signal Transduction

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.