최한곤
2018-08-31T08:06:14Z
2018-08-31T08:06:14Z
2009-03
VASCULAR PHARMACOLOGY, v. 50, No. 3-4, Page. 123-131
1537-1891
https://www.sciencedirect.com/science/article/pii/S1537189108001432
https://repository.hanyang.ac.kr/handle/20.500.11754/74703
Angiogenesis plays a critical role in the pathogenesis of malignant tumor growth and metastases. Since cyclooxygenase (COX)-2 expression is positively correlated with vascular endothelial growth factor (VEGF) expression and enhanced angiogenesis, COX-2 inhibitors have been focused on as angiogenesis-inhibiting drugs that may offer a complementary modality to classical strategies for cancer therapy. In this study, we evaluated the potential antiangiogenic effects of 1-furan-2-yl-3-pyridin-2-yl-propenone (FPP-3), a dual COX/5-LOX inhibitor. In HT1080 cancer cells, FPP-3 significantly suppressed release of VEGF as well as activation of NF-kappa B. a transcriptional factor required for VEGF expression. In a chick chorioallantoic membrane (CAM) assay, FPP-3 dose-dependently suppressed VEGF- and MCF-7 human breast cancer cell-induced angiogenesis. In experiments with human umbilical vein endothelial cells (HUVECs), FPP-3 dose-dependently decreased not only the cell survival and proliferation but also the tube formation and invasion using Matrigel-coated plates. Such antiangiogenic activity correlated with suppression of VEGF-induced matrix metalloproteinase (MMP)-2 expression, reactive oxygen species (ROS) production, and extracellularly regulated kinase (ERK) phosphorylation. Furthermore, in contrast to the case of NS398, a selective COX-2 inhibitor, FPP-3 did not alter the ratio of tissue factor (TF)/tissue factor pathway inhibitor (TFPI) expression, a coagulation index. These results indicate that FPP-3 could be used as an effective antiangiogenic agent without the risk of developing thrombotic complications. (c) 2008 Elsevier Inc. All rights reserved.
This work was supported by grant no. RT104-01-04, from the Regional Technology Innovation Program of the Ministry of Commerce, Industry, and Energy (MOCIE).
en_US
ELSEVIER SCIENCE INC
Propenone
COX-2
Tumor angiogenesis
ROS
pERK
Tissue factor
The anti-angiogenic effects of 1-furan-2-yl-3-pyridin-2-yl-propenone are mediated through the suppression of both VEGF production and VEGF-induced signaling
Article
3-4
50
10.1016/j.vph.2008.11.006
123-131
VASCULAR PHARMACOLOGY
Park, Byung Chul
Park, Su-Young
Lee, Jong-Suk
Mousa, Shaker A
Kim, Jong Tae
Kwak, Mi-Kyoung
Kang, Keon Wook
Lee, Eung-Seok
Choi, Han Gon
Yong, Chul Soon
Kim, Jung-Ae
2009214177
E
COLLEGE OF PHARMACY[E]
DEPARTMENT OF PHARMACY
hangon