Anti-angiogenic effect of furanodiene on HUVECs in vitro and on zebrafish in vivo
- Authors
- Zhong, Z.F., Hoi, P.M., Wu, G.S., Xu, Z.T., Tan, W., Chen, X.P., Cui, L., Wu, T., and Wang, Y.T.
- ID
- ZDB-PUB-110920-16
- Date
- 2012
- Source
- Journal of ethnopharmacology 141(2): 721-727 (Journal)
- Registered Authors
- Keywords
- furanodiene, anti-angiogenesis, invasion, migration, tube formation, zebrafish
- MeSH Terms
-
- Intercellular Adhesion Molecule-1/metabolism
- Proto-Oncogene Protein c-fli-1/genetics
- Heterocyclic Compounds, 2-Ring/isolation & purification
- Heterocyclic Compounds, 2-Ring/pharmacology*
- Medicine, Chinese Traditional
- Green Fluorescent Proteins/biosynthesis
- Green Fluorescent Proteins/genetics
- Animals, Genetically Modified
- Blotting, Western
- Drugs, Chinese Herbal/isolation & purification
- Drugs, Chinese Herbal/pharmacology*
- Mitogen-Activated Protein Kinase 1/metabolism
- Cell Proliferation/drug effects
- Dose-Response Relationship, Drug
- Proto-Oncogene Proteins c-akt/metabolism
- Tyrosine
- Curcuma*/chemistry
- Threonine
- Zebrafish/embryology
- Zebrafish/genetics
- Zebrafish/metabolism
- Neovascularization, Physiologic/drug effects*
- Plants, Medicinal
- Cell Differentiation/drug effects
- Wound Healing/drug effects
- Mitogen-Activated Protein Kinase 3/metabolism
- Furans/isolation & purification
- Furans/pharmacology*
- Vascular Endothelial Growth Factor A/metabolism
- Cell Movement/drug effects
- Angiogenesis Inhibitors/isolation & purification
- Angiogenesis Inhibitors/pharmacology*
- Humans
- Antineoplastic Agents, Phytogenic/isolation & purification
- Antineoplastic Agents, Phytogenic/pharmacology*
- Human Umbilical Vein Endothelial Cells/drug effects*
- Human Umbilical Vein Endothelial Cells/metabolism
- Class Ia Phosphatidylinositol 3-Kinase/metabolism
- Animals
- Phosphorylation
- Signal Transduction/drug effects
- Serine
- PubMed
- 21911050 Full text @ J. Ethnopharmacol.
Ethnopharmacological relevance
Furanodiene is an active ingredient of the traditional Chinese medicine, Rhizoma Curcumae, commonly used for the treatment of cancer in China.
Aim of the study
To investigate the anti-cancer property of Rhizoma Curcumae, this study describes the anti-angiogenic activities of furanodiene in human umbilical vein endothelial cells (HUVECs) in vitro and in zebrafish in vivo.
Materials and methods
HUVECs were treated with different doses of furanodiene in the presence or absence of vascular endothelial growth factor (VEGF). The anti-proliferative effect of furanodiene was measured using the XTT assay. The anti-migration and anti-invasion activities of this compound were investigated with a wound-healing migration model and a three-dimensional cell invasion model, respectively. The effects of furanodiene on HUVEC differentiation were assessed by in vitro tube formation in Matrigel™. The expression of related proteins was detected by Western blot. Morphological observations of zebrafish were evaluated in transgenic Tg (fli1: EGFP) zebrafish embryos.
Results
Our results showed that furanodiene exposure could significantly inhibit the proliferation of HUVECs in a dose-dependent manner and inhibit VEGF-induced proliferation at a low dose. Relative to the VEGF-induced control, the number of invading and migrating cells was significantly reduced in the furanodiene-treated groups. Furanodiene also dramatically suppressed tube formation and p-Akt (Ser473), p-Erk 1/2 (Thr202/Tyr204), ICAM-1, p-p85 (Ser428) as well as p85 protein expression. Furthermore, exposure to furanodiene inhibited angiogenesis in the zebrafish model.
Conclusions
This study demonstrated that furanodiene exposure exhibits a potential anti-angiogenic effect through suppression of endothelial cell growth, invasion, migration and tube formation via regulation of the PI3K pathway. This potential anti-angiogenic effect of furanodiene may play an important role in the anti-tumor activity of the traditional Chinese medicine, Rhizoma Curcumae.