Toxicarioside A inhibits SGC-7901 proliferation,migration and invasion via NF-κB/bFGF signaling

AIM:To investigate the inhibitory role of toxicarioside A on the gastric cancer cell line human gastric cancer cell line(SGC-7901) and determine the underlying molecular mechanism.METHODS:After SGC-7901 cells were treated with toxicarioside A at various concentrations(0.5,1.5,4.5,9.0 μg/mL) for 24 h or 48 h,cell viability was determined by 3-(4,5-dimethyl-thiazol-2-yl)-2,5-diphenyl2H-tetrazolium bromide assay,and the motility and invasion of tumor cells were assessed by the Transwell chamber assay.Immunofluorescence staining,reverse transcription polymerase chain reaction and Western blotting were performed to detect the expression of basic fibroblast growth factor(bFGF) and fibroblast growth factor receptor-1(FGFR1),and nuclear factorkappa B(NF-κB) activation was examined by electrophoretic mobility shift assay.RESULTS:The results showed that toxicarioside A was capable of reducing cell viability,inhibiting cell growth,and suppressing cell migration and invasion activities in a time-and dose-dependent manner in SGC-7901 cells.Further analysis revealed that not only the expression of bFGF and its high-affinity receptor FGFR1 but also the NF-κB-DNA binding activity were effectively blocked by toxicarioside A in a dose-dependent manner compared with the control group(P < 0.05 or P < 0.01).Interestingly,application of the NF-κB specific inhibitor,pyrrolidinedithiocarbamate(PDTC),to SGC-7901 cells significantly potentized the toxicarioside A-induced down-regulation of bFGF compared with the control group(P < 0.05).CONCLUSION:These findings suggest that toxicarioside A has an anti-gastric cancer activity and this effect may be achieved partly through down-regulation of NF-κB and bFGF/FGFR1 signaling.

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

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.

A new cytotoxic cardenolide from the latex of Antiaris toxicaria

A new cardenolide, toxicarioside E （1）, was isolated from the latex ofAntiaris toxicaria （Pers.） Lesch （Moraceae）. Its structure was elucidated on the basis of spectral data and chemical evidence. Compound 1 showed significant cytotoxicity against K562 and SGC-7901 cell lines in vitro by MTT method with the IC50 value of 0.026 and 0.027 μg/mL, respectively.

见血封喉乳汁中的化学成分研究

从海南产见血封喉[Antiaris toxicaria(Pers.)Lesch.]乳汁的乙醇提取物中分离得到6个化合物,经现代波谱技术,包括红外、一维、二维核磁共振谱和高分辨质谱,上述化合物的结构分别鉴定为:toxicarioside I(1),毒毛旋花子苷元(2),杠柳苷元(3),(3β,5α,1β,17α)-3,14-二羟基孕甾-20-酮(4),α-生育酚(5)和3,4,5-三甲氧基苯酚(6),其中化合物1为新的强心苷,化合物4和5为首次从该植物中分离得到.经MTT法进行体外细胞毒活性测试,结果表明化合物1～3对慢性髓原白血病细胞(K562)、人胃癌细胞(SGC-7901)和人肝癌细胞(SMMC-7721)的增殖显示了抑制活性,其IC_(50)值范围为0.001～12.3μmol·L^(-1).