Toxicarioside A,isolated from tropical Antiaris toxicaria,blocks endoglin/TGF-βsignaling in a bone marrow stromal cell line

• Published in: Asian Pacific journal of tropical medicine 2012-02, Vol.5 (2), p.91-97
• Main Authors: Li, Yue-Nan, Huang, Feng-Ying, Mei, Wen-Li, Dai, Hao-Fu, Guo, Jun-Li, Tan, Guang-Hong, Zhou, Peng
• Format: Article
• Language: English
• Subjects: Antiaris; Antigens, CD - metabolism; Blotting, Northern; Blotting, Western; Bone Marrow Cells - drug effects; Bone Marrow Cells - metabolism; Cardenolides - pharmacology; Cell; Cell Line; Cell Proliferation; Endoglin; factor-β; growth; Humans; Male; pathway; proliferation; Receptors, Cell Surface - antagonists & inhibitors; Receptors, Cell Surface - metabolism; Signal; Signal pathway; Signal Transduction - drug effects; Smad1 Protein - drug effects; Smad1 Protein - metabolism; Smad2 Protein - drug effects; Smad2 Protein - metabolism; Stromal Cells - drug effects; Toxicarioside; Toxicarioside A; Transforming; Transforming Growth Factor beta - antagonists & inhibitors; Transforming Growth Factor beta - metabolism; Transforming growth factor-β
• ISSN: 1995-7645; 2352-4146
• DOI: 10.1016/S1995-7645(12)60002-9

<正>Objective:To investigate possible mechanism of toxicarioside A in HS-5 bone stromal cells.Methods:HS-5 bone stromal cells were cultured in media supplemented with various concentrations of toxicarioside A or control DMSO(not treatment).Endoglin and TGF-βwere detected by Northern and Western blot analysis and quantified in a standard method. Downstream molecules of endoglin and TGF-β(Smad1,Smad2 and their active phosphorylated counterparts,pSmad1 and pSmad2) were also detected and quantified by Western blot analysis. In addition,cell proliferation assay and small interfering RNA(siRNA) against endoglin were used to certificate the function of endolgin in the HS-5 cells.Results:Compared with the not treated(0μg/mL) or DMSO treated control HS-5 cells,HS-5 cells treated with toxicarioside A were found significant attenuation of endolgin and TGF-βexpression.Significant inhibition of cell proliferation was also found in the HS-5 cells treated with toxicarioside A.ALK1-related Smad1 and ALK5-related Smad2 were decreased in HS-5 cells treated with toxicarioside A.In addition,phosphorylated Smad1(pSmad1) and Smad2(pSmad2) were also found attenuation in toxicarioside A-treated HS-5 cells.RNA interference showed that blockage of endoglin by siRNA also decreased Smad1 and Smad2 expression in HS-5 cells.Conclusions:Our results indicate that toxicarioside A can influence bone marrow stromal HS-5’s function and inhibit HS-5 cell proliferation by alteration of endoglin-related ALK1(Smad1) and ALK5(Smad2) signaling.