Anti-angiogenic effect of furanodiene on HUVECs in vitro and on zebrafish in vivo.

Abstract

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.

• Authors: Zhang-Feng Zhong, Pui-Man Hoi, Guo-Sheng Wu, Zeng-Tao Xu, Wen Tan, Xiu-Ping Chen, Liao Cui, Tie Wu, Yi-Tao Wang
• Journal: Journal of ethnopharmacology (J Ethnopharmacol) Vol. 141 Issue 2 Pg. 721-7 (Jun 01 2012) ISSN: 1872-7573 [Electronic] Ireland
• PMID: 21911050 (Publication Type: Journal Article, Research Support, U.S. Gov't, Non-P.H.S.)
• Copyright: Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Chemical References

• Angiogenesis Inhibitors
• Antineoplastic Agents, Phytogenic
• Drugs, Chinese Herbal
• Furans
• Heterocyclic Compounds, 2-Ring
• Proto-Oncogene Protein c-fli-1
• Vascular Endothelial Growth Factor A
• enhanced green fluorescent protein
• Intercellular Adhesion Molecule-1
• Green Fluorescent Proteins
• furanodiene
• Threonine
• Tyrosine
• Serine
• Class Ia Phosphatidylinositol 3-Kinase
• Proto-Oncogene Proteins c-akt
• MAPK1 protein, human
• Mitogen-Activated Protein Kinase 1
• Mitogen-Activated Protein Kinase 3

Topics

• Angiogenesis Inhibitors (isolation & purification, pharmacology)
• Animals
• Animals, Genetically Modified
• Antineoplastic Agents, Phytogenic (isolation & purification, pharmacology)
• Blotting, Western
• Cell Differentiation (drug effects)
• Cell Movement (drug effects)
• Cell Proliferation (drug effects)
• Class Ia Phosphatidylinositol 3-Kinase (metabolism)
• Curcuma (chemistry)
• Dose-Response Relationship, Drug
• Drugs, Chinese Herbal (isolation & purification, pharmacology)
• Furans (isolation & purification, pharmacology)
• Green Fluorescent Proteins (biosynthesis, genetics)
• Heterocyclic Compounds, 2-Ring (isolation & purification, pharmacology)
• Human Umbilical Vein Endothelial Cells (drug effects, metabolism)
• Humans
• Intercellular Adhesion Molecule-1 (metabolism)
• Medicine, Chinese Traditional
• Mitogen-Activated Protein Kinase 1 (metabolism)
• Mitogen-Activated Protein Kinase 3 (metabolism)
• Neovascularization, Physiologic (drug effects)
• Phosphorylation
• Plants, Medicinal
• Proto-Oncogene Protein c-fli-1 (genetics)
• Proto-Oncogene Proteins c-akt (metabolism)
• Serine
• Signal Transduction (drug effects)
• Threonine
• Tyrosine
• Vascular Endothelial Growth Factor A (metabolism)
• Wound Healing (drug effects)
• Zebrafish (embryology, genetics, metabolism)