title: Biflavone Ginkgetin, a Novel Wnt Inhibitor, Suppresses the Growth of Medulloblastoma.
abstract: 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 IC50value around 5.92 μM 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 β-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 anti-medulloblastoma candidate.
authors.affiliation: State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming, 650201, Yunnan, China.
authors.forename: Zhen-Nan
authors.initials: ZN
authors.lastname: Ye
authors.forename: Mu-Yuan
authors.initials: MY
authors.lastname: Yu
authors.forename: Ling-Mei
authors.initials: LM
authors.lastname: Kong
authors.forename: Wei-Hua
authors.initials: WH
authors.lastname: Wang
authors.forename: Yuan-Feng
authors.initials: YF
authors.lastname: Yang
authors.forename: Jie-Qing
authors.initials: JQ
authors.lastname: Liu
authors.forename: Ming-Hua
authors.initials: MH
authors.lastname: Qiu
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
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