Naunyn-Schmiedeberg's Archives of Pharmacology

, Volume 385, Issue 1, pp 39–49 | Cite as

Bp5250 inhibits vascular endothelial growth factor-induced angiogenesis and HIF-1α expression on endothelial cells

  • Kuan-Ting Lin
  • Jin-Cherng Lien
  • Ching-Hu Chung
  • Sheng-Chu Kuo
  • Tur-Fu Huang


Angiogenesis plays a critical role in many physiological and pathological phenomena. A number of anti-angiogenesis drugs have been used in the clinical treatment of diseases such as malignant tumors and macular degeneration. Vascular endothelial growth factor (VEGF), the major pro-angiogenesis factor, is known to stimulate various steps of endothelial angiogenic activity, such as proliferation, migration, and differentiation into vessel-like tubes. In this study, we tested the effects of bp5250 on the angiogenesis of human umbilical endothelial cells (HUVECs). Bp5250 suppressed VEGF-induced endothelial cell proliferation by triggering apoptosis, and reduced endothelial cell migration toward VEGF. Bp5250 also decreased VEGF-stimulated tube formation and rat aortic ring sprouting on Matrigel in a concentration-dependent manner. In the VEGF-activated signaling pathways, bp5250 decreased the phosphorylation of ERK, p38, PI3K-AKT, Src, and FAK and also reduced the activation of the cytoskeleton-associated Rho family, all in a concentration-dependent manner. Bp5250 also attenuated the hypoxia-inducible factor-1α (HIF-1α) and VEGF-stimulated mRNA expression of HUVECs under the hypoxic condition. In vivo, angiogenesis was restrained by a daily intraperitoneal administration of bp5250 in a dose-dependent manner (1–3 mg/kg/d) in the Matrigel plug implantation assay. These results indicate that bp5250 is a potential candidate for developing anti-angiogenic agents.


Angiogenesis Vascular endothelial growth factor Endothelial cell Hypoxia-inducible factor-1α 



This work was supported by grants from the National Science Council (NSC97-2323-B-002-008, NSC98-2323-B-002-009, NSC99-2323-B-002-004 and NSC99-2320-B-039-010-MY3) of Taiwan.

Conflict of interest

The authors state that there is no conflict of interest.


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Copyright information

© Springer-Verlag 2011

Authors and Affiliations

  1. 1.Graduate Institute of Pharmacology, College of MedicineNational Taiwan UniversityTaipeiTaiwan
  2. 2.Graduate Institute of Pharmaceutical ChemistryChina Medical UniversityTaichungTaiwan
  3. 3.Institute of Pharmacology and ToxicologyTzu Chi UniversityHualienTaiwan

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