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.

Cytochalasin D,a tropical fungal metabolite,inhibits CT26 tumor growth and angiogenesis

Objective:To investigate whether eytochalasin D can induce antitumor activities in a tumor model.Methods:Murine CT26 colorectal carcinoma cells were cultured hi vitro and cytochalasin D was used as a cytotoxic agent to detect its capabilities of inhibiting CT26 cell proliferation and inducing cell apoptosis by MTT and a TUNEL-based apoptosis assay.Murine CT26 tumor model was established to observe the tumor growth and survival time.Tumor tissues were used to detect the mierovessel density by immunohistochemistry.In addition,alginate encapsulated tumor cell assay was used to quantify the tumor angiogenesis in vivo.Results:Cytochalasin D inhibited CT26 tumor cell proliferation in lime and dose dependent manner and induced signiflcanl CT26 cell apoptosis,which almost reached the level induced by the positive control nuclease.The optimum effective dose of cytochalasin D for in vivo therapy was about 50 mg/kg.Cytochalasin D in vivo treatment significandy inhibited tumor growth and prolonged the survival times in CT26 tumor-bearing mice.The results of immunohistochemistry analysis and alginate encapsulation assay indicated that the cytochalasin D could effectively inhibited tumor angiogenesis. Conclusions:Cytochalasin D inhibits CT26 tumor growth potentially through inhibition of cell proliferation,induction of cell apoptosis and suppression of tumor angiogenesis.

Two new tremulane sesquiterpenes from a mangrove endophytic fungus,Coriolopsis sp.J5

Two new tremulane sesquiterpenes coriolopsin A（1） and coriolopsin B（2）,together with two known ones conocenol C（3） and ceriponol E（4）,were isolated from the fermentation extract of endophytic fungus Coriolopsis sp.J5 from Ceriops tagal.The structures and absolute configuration of compounds 1 and 2 were determined based on HR-ESI-MS and spectroscopic data（IR,UV,1D,2D NMR and X-ray crystallographic analysis）.