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Tryptanthrin inhibits angiogenesis by targeting the VEGFR2-mediated ERK1/2 signalling pathway.
- Source :
-
PloS one [PLoS One] 2013 Dec 16; Vol. 8 (12), pp. e82294. Date of Electronic Publication: 2013 Dec 16 (Print Publication: 2013). - Publication Year :
- 2013
-
Abstract
- Angiogenesis is a key step for tumour growth and metastasis, and anti-angiogenesis has been proposed as an important strategy for cancer therapy. Tryptanthrin is a weakly basic alkaloid isolated from the dried roots of medicinal indigo plants and has been shown to possess anti-tumour activities on various cancer cell types. This study aims to investigate the in vitro and in vivo anti-angiogenic activities of tryptanthrin and to unravel its underlying molecular action mechanisms. Our results show that tryptanthrin inhibited the in vitro proliferation, migration, and tube formation of the human microvascular endothelial cells (HMEC-1) in a concentration-dependent manner and significantly suppressed angiogenesis in Matrigel plugs in mice. Mechanistic studies indicated that tryptanthrin reduced the expression of several pro-angiogenic factors (Ang-1, PDGFB and MMP2). Tryptanthrin was also found to suppress the VEGFR2-mediated ERK1/2 signalling pathway in HMEC-1 cells and molecular docking simulation indicated that tryptanthrin could bound to the ATP-binding site of VEGFR2. Collectively, the present study demonstrated that tryptanthrin exhibited both in vitro and in vivo anti-angiogenic activities by targeting the VEGFR2-mediated ERK1/2 signalling pathway and might have therapeutic potential for the treatment of angiogenesis-related diseases.
- Subjects :
- Angiogenesis Inhibitors pharmacology
Animals
Cell Line
Cell Proliferation drug effects
Drugs, Chinese Herbal pharmacology
Endothelial Cells drug effects
Endothelial Cells metabolism
Humans
Mice
Neovascularization, Pathologic metabolism
Quinazolines pharmacology
Wound Healing drug effects
Angiogenesis Inhibitors therapeutic use
Drugs, Chinese Herbal therapeutic use
MAP Kinase Signaling System drug effects
Neovascularization, Pathologic drug therapy
Quinazolines therapeutic use
Vascular Endothelial Growth Factor Receptor-2 metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1932-6203
- Volume :
- 8
- Issue :
- 12
- Database :
- MEDLINE
- Journal :
- PloS one
- Publication Type :
- Academic Journal
- Accession number :
- 24358167
- Full Text :
- https://doi.org/10.1371/journal.pone.0082294