Medulloblastoma(MB)is a form of malignant brain tumor that predominantly arises in infants and children,of which approximately 25%is due to upregulation of canonical Wnt pathway with mainly mutations in CTNNB1.Therefo...Medulloblastoma(MB)is a form of malignant brain tumor that predominantly arises in infants and children,of which approximately 25%is due to upregulation of canonical Wnt pathway with mainly mutations in CTNNB1.Therefore,Wnt inhibitors could offer rational therapeutic strategies and chemoprevention for this malignant cancer.In our present study,we undertook a screening for antagonists of Wnt signaling from 600 natural compounds,and identified Ginkgetin,a biflavone isolated from Cephalotaxus fortunei var.alpina.Ginkgetin inhibited Wnt pathway with an IC50 value around 5.92 lM and structure–activity relationship analysis suggested the methoxy group in Ginkgetin as a functional group.Biflavone Ginkgetin showed obvious cytotoxicity in Daoy and D283 MB cells.Cell cycle analysis by flow cytometry showed that Ginkgetin induced efficiently G2/M phase arrest in Daoy cells.Further mechanism studies showed that Ginkgetin reduced the expression of Wnt target genes,including Axin2,cyclinD1 and survivin in MB cells.The phosphorylation level of b-catenin also decreased in a time-and concentration-dependent manner.Collectively,our data suggest that Ginkgetin is a novel inhibitor of Wnt signaling,and as such warrants further exploration as a promising antimedulloblastoma candidate.展开更多
The present study investigated the chemical constituents of the roots of Stellera chamaejasme(Thymelaeaceae).One new biflavone glucoside(1),along with other thirteen known compounds(2–14),was isolated by repeated col...The present study investigated the chemical constituents of the roots of Stellera chamaejasme(Thymelaeaceae).One new biflavone glucoside(1),along with other thirteen known compounds(2–14),was isolated by repeated column chromatographic methods and their structures were elucidated on the basis of spectral analyses.The cytotoxic activities of selected compounds were evaluated against four human cancer cell lines(A549,BEL-7402,HCT-116,and MDA-MB-231) by the SRB assay method.Compound 9 showed remarkable cytotoxicity against BEL-7402 with IC50 value being 0.65 μg·mL-1; compounds 7,8,and 12 exhibited significant cytotoxic activity against A549 with IC50 values being 2.38,1.57,and 2.35 μg·m L-1,respectively.展开更多
基金the hundreds top talents program from Chinese Academy of Sciences,the NSFC(Nos.81173076,81403050)the projects of science and technology of Yunnan Province(2009C1120,2013FA047).
文摘Medulloblastoma(MB)is a form of malignant brain tumor that predominantly arises in infants and children,of which approximately 25%is due to upregulation of canonical Wnt pathway with mainly mutations in CTNNB1.Therefore,Wnt inhibitors could offer rational therapeutic strategies and chemoprevention for this malignant cancer.In our present study,we undertook a screening for antagonists of Wnt signaling from 600 natural compounds,and identified Ginkgetin,a biflavone isolated from Cephalotaxus fortunei var.alpina.Ginkgetin inhibited Wnt pathway with an IC50 value around 5.92 lM and structure–activity relationship analysis suggested the methoxy group in Ginkgetin as a functional group.Biflavone Ginkgetin showed obvious cytotoxicity in Daoy and D283 MB cells.Cell cycle analysis by flow cytometry showed that Ginkgetin induced efficiently G2/M phase arrest in Daoy cells.Further mechanism studies showed that Ginkgetin reduced the expression of Wnt target genes,including Axin2,cyclinD1 and survivin in MB cells.The phosphorylation level of b-catenin also decreased in a time-and concentration-dependent manner.Collectively,our data suggest that Ginkgetin is a novel inhibitor of Wnt signaling,and as such warrants further exploration as a promising antimedulloblastoma candidate.
基金supported by the National Natural Science Foundation of China(Nos.81001369 and 31170327)the Fundamental Research Funds for the Central Universities(No.2000219078)of China
文摘The present study investigated the chemical constituents of the roots of Stellera chamaejasme(Thymelaeaceae).One new biflavone glucoside(1),along with other thirteen known compounds(2–14),was isolated by repeated column chromatographic methods and their structures were elucidated on the basis of spectral analyses.The cytotoxic activities of selected compounds were evaluated against four human cancer cell lines(A549,BEL-7402,HCT-116,and MDA-MB-231) by the SRB assay method.Compound 9 showed remarkable cytotoxicity against BEL-7402 with IC50 value being 0.65 μg·mL-1; compounds 7,8,and 12 exhibited significant cytotoxic activity against A549 with IC50 values being 2.38,1.57,and 2.35 μg·m L-1,respectively.
