ReferenceID 404
A Systems Pharmacology Approach Uncovers Wogonoside as an Angiogenesis Inhibitor of Triple-Negative Breast Cancer by Targeting Hedgehog Signaling
Cell Chem Biol
Triple-negative breast cancer (TNBC) is an aggressive and heterogeneous disease that lacks clinically actionable genetic alterations that limit targeted therapies. Here we explore a systems pharmacology approach that int
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Record Fields
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- Reference Id
- 404
- Evidence Id
- 16994
- Core Evidence Id
- 16994
- Source Reference Id
- 779
- Herb2 Reference Id
- HBREF001344
- Subject Paper Key
- HBIN048376_31178408
- Pubmed Id
- 31178408
- Doi
- 10.1016/j.chembiol.2019.05.004
- Paper Title
- A Systems Pharmacology Approach Uncovers Wogonoside as an Angiogenesis Inhibitor of Triple-Negative Breast Cancer by Targeting Hedgehog Signaling
- Paper Abstract
- Triple-negative breast cancer (TNBC) is an aggressive and heterogeneous disease that lacks clinically actionable genetic alterations that limit targeted therapies. Here we explore a systems pharmacology approach that integrates drug-target networks and large-scale genomic profiles of TNBC and identify wogonoside, one of the major active flavonoids, as a potent angiogenesis inhibitor. We validate that wogonoside attenuates cell migration, tube formation, and rat aorta microvessel outgrowth, and reduces formation of blood vessels in chicken chorioallantoic membrane and TNBC cell-induced Matrigel plugs. In addition, wogonoside inhibits growth and angiogenesis in TNBC cell xenograft models. This network-based approach predicts, and we empirically validate, wogonoside's antiangiogenic effects resulting from vascular endothelial growth factor secretion. Mechanistically, wogonoside inhibits Gli1 nuclear translocation and transcriptional activities associated with Hedgehog signaling, by promoting Smoothened degradation in a proteasome-dependent mechanism. This study offers a powerful, integrated, systems pharmacology-based strategy for oncological drug discovery and identifies wogonoside as a potential TNBC angiogenesis inhibitor.
- Journal
- Cell Chem Biol
- Publish Year
- 2019
- Experiment Subject
- tnbc cell xenograft models,rat
- Experiment Type
- Animal & Cell Experiment
- Phenotype Related
- Triple-negative Breast Cancer
- Paper Title Cn
- Paper Title En
- A Systems Pharmacology Approach Uncovers Wogonoside as an Angiogenesis Inhibitor of Triple-Negative Breast Cancer by Targeting Hedgehog Signaling
- Bilingual Status
- semi_complete