Back to Search
Start Over
Cucurbitacin E, a tetracyclic triterpenes compound from Chinese medicine, inhibits tumor angiogenesis through VEGFR2-mediated Jak2-STAT3 signaling pathway
- Source :
- Carcinogenesis. 31(12)
- Publication Year :
- 2010
-
Abstract
- Cucurbitacin E (CuE, α-elaterin), a tetracyclic triterpenes compound from folk traditional Chinese medicine plants, has been shown to inhibit cancer cell growth, inflammatory response and bilirubin-albumin binding. However, the effects of CuE on tumor angiogenesis and its potential molecular mechanism are still unknown. Here, we demonstrated that CuE significantly inhibited human umbilical vascular endothelial cell (HUVEC) proliferation, migration and tubulogenesis in vitro and blocked angiogenesis in chick embryo chorioallantoic membrane assay and mouse corneal angiogenesis model in vivo. Furthermore, we found that CuE remarkably induced HUVEC apoptosis, inhibited tumor angiogenesis and suppressed human prostate tumor growth in xenograft tumor model. Finally, we showed that CuE blocked vascular endothelial growth factor receptor (VEGFR) 2-mediated Janus kinase (Jak) 2-signal transducer and activator of transcription (STAT) 3 signaling pathway in endothelial cells and suppressed the downstream protein kinases, such as extracellular signal-regulated kinase and p38 mitogen-activated protein kinases. Therefore, our studies provided the first evidence that CuE inhibited tumor angiogenesis by inhibiting VEGFR2-mediated Jak-STAT3 and mitogen-activated protein kinases signaling pathways and CuE is a potential candidate in angiogenesis-related disease therapy.
- Subjects :
- Male
STAT3 Transcription Factor
Cancer Research
Angiogenesis
p38 mitogen-activated protein kinases
Active Transport, Cell Nucleus
Angiogenesis Inhibitors
Apoptosis
Chick Embryo
Pharmacology
p38 Mitogen-Activated Protein Kinases
chemistry.chemical_compound
Mice
Medicine
Animals
Humans
Phosphorylation
Extracellular Signal-Regulated MAP Kinases
Cells, Cultured
Cucurbitacin E
Janus kinase 2
biology
Neovascularization, Pathologic
Kinase
business.industry
General Medicine
Neoplasms, Experimental
Janus Kinase 2
Vascular Endothelial Growth Factor Receptor-2
Xenograft Model Antitumor Assays
Triterpenes
Endothelial stem cell
Mice, Inbred C57BL
chemistry
Cancer research
biology.protein
Signal transduction
Janus kinase
business
Signal Transduction
Subjects
Details
- ISSN :
- 14602180
- Volume :
- 31
- Issue :
- 12
- Database :
- OpenAIRE
- Journal :
- Carcinogenesis
- Accession number :
- edsair.doi.dedup.....2d50d623819b52f867aeb42fb9966684