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 extraction of anticancer agents from medicinal plants represents a highly promising research frontier.Ginkgetin,a natural biflavone,is one of the effective pharmacological components of Ginkgo biloba leaves(GBLs)....The extraction of anticancer agents from medicinal plants represents a highly promising research frontier.Ginkgetin,a natural biflavone,is one of the effective pharmacological components of Ginkgo biloba leaves(GBLs).This natural product exhibits significant anti-cancer efficacy against a variety of cancer cells in vitro and demonstrates a potent inhibitory impact on tumor growth in vivo without severe toxicity.Additionally,ginkgetin synergizes with chemo-therapy drugs or adjuvant therapies to potentiate antitumor effects and reduce side effects.These compelling findings underscore Ginkgetin's potential as a promising candidate for novel anti-cancer therapeutics.Therefore,this review systematically summarizes the remarkable anticancer effects of ginkgetin and elucidates its multifaceted anticancer mechanisms,including inducing cell cycle arrest,triggering programmed cell death,and preventing inva-sion and angiogenesis.From a molecular mechanism perspective,ginkgetin exerts anti-cancer activity by modulat-ing critical signaling pathways(e.g.JAK/STAT,Wnt/β-catenin,AKT/GSK-3β,MAPKs,and estrogen receptor pathways)and regulating microRNA expression levels.Furthermore,target identification,research limitations,future directions,and application prospects are comprehensively outlined,aiming to facilitate the clinical translation of ginkgetin.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 Science and Technology Development Fund,Macao SAR(File No.0015-2022-A1 and 005/2023/SKL)University of Macao(File No.MYRG-GRG2024-00113-ICMS-UMDF)awarded to Jin-Jian Lu.Additionallysupported by the National Natural Science Foundation of China(File No.82403357)awarded to Ting Li.
文摘The extraction of anticancer agents from medicinal plants represents a highly promising research frontier.Ginkgetin,a natural biflavone,is one of the effective pharmacological components of Ginkgo biloba leaves(GBLs).This natural product exhibits significant anti-cancer efficacy against a variety of cancer cells in vitro and demonstrates a potent inhibitory impact on tumor growth in vivo without severe toxicity.Additionally,ginkgetin synergizes with chemo-therapy drugs or adjuvant therapies to potentiate antitumor effects and reduce side effects.These compelling findings underscore Ginkgetin's potential as a promising candidate for novel anti-cancer therapeutics.Therefore,this review systematically summarizes the remarkable anticancer effects of ginkgetin and elucidates its multifaceted anticancer mechanisms,including inducing cell cycle arrest,triggering programmed cell death,and preventing inva-sion and angiogenesis.From a molecular mechanism perspective,ginkgetin exerts anti-cancer activity by modulat-ing critical signaling pathways(e.g.JAK/STAT,Wnt/β-catenin,AKT/GSK-3β,MAPKs,and estrogen receptor pathways)and regulating microRNA expression levels.Furthermore,target identification,research limitations,future directions,and application prospects are comprehensively outlined,aiming to facilitate the clinical translation of ginkgetin.
