Antrodia cinnamomea produces anti-angiogenic effects by inhibiting the VEGFR2 signaling pathway. (28th June 2018)

• Record Type: Journal Article
• Authors: Huang, Tsung-Teng; Lan, Ying-Wei; Ko, Yun-Fei; Chen, Chuan-Mu; Lai, Hsin-Chih; Ojcius, David M.; Martel, Jan; Young, John D.; Chong, Kowit-Yu
• Is Part Of: Journal of ethnopharmacology. Volume 220(2018)
• Page Start: 239
• Page End: 249
• Publication Date: 2018-06-28
• Subjects: Antrodia cinnamomea -- Anti-angiogenic activity -- Endothelial cells -- VEGFR2 -- STAT3; Ethnopharmacology -- Periodicals; Pharmacognosy -- Periodicals; Herbs -- Periodicals; Herbs -- Periodicals; Pharmacognosy -- Periodicals; Pharmacognosie -- Périodiques; Herbes -- Périodiques; 615.1
• DOI: 10.1016/j.jep.2018.03.041
• Languages: English
• ISSNs: 0378-8741

Abstract

Abstract: Ethnopharmacological relevance: The medicinal mushroom Antrodia cinnamomea has been used to treat cancer but its anti-angiogenic effects have not been studied in detail. Aim of the study: The main objective of this study was to determine the molecular mechanism of activity underlying the anti-angiogenic effects of A. cinnamomea. Materials and methods: The effects of an A. cinnamomea ethanol extract (ACEE) on cell migration and microvessel formation were investigated in endothelial cells in vitro and Matrigel plugs implanted into mice in vivo . Activation of intracellular signaling pathways was examined using Western blotting. Protein expression was assessed using immunohistochemistry in a mouse model of lung metastasis. Results: We show that treatment with ACEE inhibits cell migration and tube formation in human umbilical vein endothelial cells (HUVECs). ACEE suppresses phosphorylation of vascular endothelial growth factor receptor 2 (VEGFR2) and expression of pro-angiogenic kinases in vascular endothelial growth factor (VEGF)-treated HUVECs, in addition to reducing expression of Janus kinase 2 (JAK2) and phosphorylation of signal transducer and activator of transcription 3 (STAT3). ACEE treatment inhibits VEGF-induced microvessel formation in Matrigel plugs in vivo . In addition, ACEE significantly reduces VEGFR2 expression in Lewis lung carcinoma cells and downregulates the expression of cluster of differentiation 31 (CD31) and VEGFR2 in murine lung metastases. Conclusion: These results indicate that A. cinnamomea produces anti-angiogenic effects by inhibiting the VEGFR2 signaling pathway. Graphical abstract: