Arsenic trioxide promotes senescence and regulates the balance of adipogenic and osteogenic differentiation in human mesenchymal stem cells

• Published in: Acta biochimica et biophysica Sinica 2011-03, Vol.43 (3), p.204-209
• Main Authors: Cheng, Huanchen, Qiu, Lin, Zhang, Hao, Cheng, Mei, Li, Wei, Zhao, Xuefei, Liu, Keyu, Lei, Lei, Ma, Jun
• Format: Article
• Language: English
• Subjects: Adipogenesis - drug effects; Aging - drug effects; Arsenicals - pharmacology; Bone Marrow Cells - cytology; Bone Marrow Cells - drug effects; Bone Marrow Cells - metabolism; CCAAT-Enhancer-Binding Protein-alpha - drug effects; CCAAT-Enhancer-Binding Protein-alpha - metabolism; Cell Differentiation - drug effects; Cells, Cultured - drug effects; Cyclin-Dependent Kinase Inhibitor p21 - drug effects; Cyclin-Dependent Kinase Inhibitor p21 - metabolism; Humans; Mesenchymal Stromal Cells - cytology; Mesenchymal Stromal Cells - drug effects; Mesenchymal Stromal Cells - metabolism; Osteogenesis - drug effects; Oxides - pharmacology; PPAR gamma - drug effects; PPAR gamma - metabolism; 三氧化二砷; 增强子结合蛋白; 成骨分化; 抗肿瘤作用; 间质干细胞; 骨髓基质细胞
• ISSN: 1672-9145; 1745-7270
• DOI: 10.1093/abbs/gmq130

Arsenic trioxide （ATO） as an anti-tumor drug could induce differentiation and apoptosis in tumor cells. Mesenchymal stem cells （MSCs） play important roles in the hematogenesis of bone marrow. Many reports have shown that the disorder of MSC adipogenic and osteo- genic differentiation occurs in some diseases. However, reports about the effects of ATO on MSCs are limited. In this study, we found that 1 μM ATO promoted MSC senescence mainly through p21, although it had no effect on apoptosis at this dose. Furthermore, ATO promoted adipogenic differentiation, but inhibited osteogenic differentiation in MSCs. Our study also showed that CCAAT/ enhancer-binding protein alpha C/EBParsenic trioxide; mesenchymal stem cells; differentiation; C/EBPα; PPAR-γ and peroxisome proliferator-activated receptor gamma PPAR might be involved in the regulation of adipogenic and osteogenic differentiation induced by ATO. Our results indicated that ATO may exert an anti-tumor effect by influencing bone marrow micro-environment. Moreover, it may regulate the adipogenic and osteogenic differentiation of MSCs.