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Updated: Sep 27, 2025
Isolation of Human Umbilical Vein Endothelial Cells HUVEC
Published on: April 28, 2007
Curcuminoids Inhibit Angiogenic Behaviors of Human Umbilical Vein Endothelial Cells via Endoglin/Smad1 Signaling
Yi-Fan Chou1,2,3, Yu-Hsuan Lan4, Jun-Han Hsiao4
1Graduate Institute of Biomedical Sciences, College of Medicine, China Medical University, Taichung 411710, Taiwan.
Background:
Angiogenesis is primarily attributed to the excessive proliferation and migration of endothelial cells. Targeting the vascular endothelial growth factor (VEGF) is therefore significant in anti-angiogenic therapy. Although these treatments have not reached clinical expectations, the upregulation of alternative angiogenic pathways (endoglin/Smad1) may play a critical role in drug (VEGF-neutralizing agents) resistance. Enhanced endoglin expression following a VEGF-neutralizing therapy (semaxanib®) was noted in patients. Treatment with an endoglin-targeting antibody augmented VEGF expression in human umbilical vein endothelial cells (HUVECs). Therefore, approaches that inhibit both the androgen and VEGF pathways enhance the HUVECs cytotoxicity and reverse semaxanib resistance. The purpose of this study was to find natural-occurring compounds that inhibited the endoglin-targeting pathway.
Methods:
Curcuminoids targeting endoglin were recognized from two thousand compounds in the Traditional Chinese Medicine Database@Taiwan (TCM Database@Taiwan) using Discovery Studio 4.5.
Results:
Our results, obtained using cytotoxicity, migration/invasion, and flow cytometry assays, showed that curcumin (Cur) and demethoxycurcumin (DMC) reduced angiogenesis. In addition, Cur and DMC downregulated endoglin/pSmad1 phosphorylation.
Conclusions:
The study first showed that Cur and DMC demonstrated antiangiogenic activity via the inhibition of endoglin/Smad1 signaling. Synergistic effects of curcuminoids (i.e., curcumin and DMC) and semaxanib on HUVECs were found. This might be attributed to endoglin/pSmad1 downregulation in HUVECs. Combination treatment with curcuminoids and a semaxanib is therefore expected to reverse semaxanib resistance.
Insights
Curcumin and demethoxycurcumin show anti-angiogenic effects by inhibiting the endoglin/Smad1 pathway. These natural compounds may reverse resistance to anti-angiogenic drugs like semaxanib.
Area of Science:
- Biochemistry
- Molecular Biology
- Pharmacology
Background:
- Angiogenesis, driven by endothelial cell proliferation and migration, is a key target for anti-angiogenic therapies like VEGF-neutralizing agents.
- Resistance to VEGF-neutralizing agents can occur through alternative pathways, such as endoglin/Smad1, which is upregulated in patients.
- Enhanced endoglin expression following semaxanib treatment suggests a role for this pathway in therapeutic resistance.
Purpose of the Study:
- To identify natural compounds that inhibit the endoglin-targeting pathway.
- To explore potential treatments for reversing resistance to VEGF-neutralizing therapies.
Main Methods:
- Screening of 2,000 compounds from the Traditional Chinese Medicine Database@Taiwan using Discovery Studio 4.5.
- Identification of curcuminoids as potential endoglin inhibitors.
- Utilizing cytotoxicity, migration/invasion, and flow cytometry assays to validate findings.
Main Results:
- Curcumin (Cur) and demethoxycurcumin (DMC) demonstrated significant anti-angiogenic activity.
- Cur and DMC were found to reduce angiogenesis by downregulating endoglin/pSmad1 phosphorylation.
- Synergistic effects were observed when combining curcuminoids with semaxanib on human umbilical vein endothelial cells (HUVECs).
Conclusions:
- Curcumin and demethoxycurcumin exhibit anti-angiogenic properties by inhibiting the endoglin/Smad1 signaling pathway.
- The combination of curcuminoids and semaxanib shows potential to reverse semaxanib resistance in HUVECs.
- This study highlights curcuminoids as promising agents for overcoming anti-angiogenic drug resistance.
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