Abstract
The growth and metastasis of human solid tumors and the development of conditions such as diabetic retinopathy, rheumatoid arthritis, inflammatory psoriasis, and others are regulated by the balance between angiogenic stimulators and inhibitors released in the angiogenic-pathological microenvironment. Vascular endothelial growth factor (VEGF), an angiogenic factor, is a potent endothelial-specific mitogen that activates endothelial cells in pathological angiogenesis. Recently, we demonstrated that caffeic acid phenethyl ester (CAPE) inhibits tumor growth, invasion, and metastasis. However, the precise molecular mechanism underlying the inhibitory effect of CAPE on VEGF-mediated angiogenesis remains unknown. Here, we show that CAPE suppressed VEGF-induced proliferation, tube formation, migration, the formation of actin stress fibers and loss of VE-cadherin at cell-cell contacts in endothelial cells, indicating the inhibition of VEGF-mediated VEGF receptor-2 (VEGFR-2) and its downstream signal activation in vitro. CAPE blocked VEGF-stimulated neovascularization in the Matrigel plugs assay, and reduced vascular permeability in mouse skin capillaries in vivo. CAPE inhibited the growth and neovascularization of primary tumor cells in C57BL/6 and BALB/c mice inoculated with Lewis lung carcinoma, colon carcinoma, and melanoma cells. These results suggest that CAPE negatively modulates VEGF-induced angiogenesis by suppressing VEGFR-2 activation, and might be a therapeutic avenue for anti-angiogenesis.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 271-282 |
| Number of pages | 12 |
| Journal | Journal of Molecular Medicine |
| Volume | 91 |
| Issue number | 2 |
| DOIs | |
| State | Published - Feb 1 2013 |
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Keywords
- Angiogenesis
- Caffeic acid phenethyl ester (CAPE)
- Vascular endothelial growth factor (VEGF)
- Vascular endothelial growth factor receptor-2 (VEGFR-2)
ASJC Scopus subject areas
- Molecular Medicine
- Drug Discovery
- Genetics(clinical)
Cite this
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CAPE suppresses VEGFR-2 activation, and tumor neovascularization and growth. / Chung, Tae Wook; Kim, Seok Jo; Choi, Hee Jung; Kwak, Choong Hwan; Song, Kwon Ho; Suh, Seok Jong; Kim, Keuk Jun; Ha, Ki Tae; Park, Young Guk; Chang, Young Chae; Chang, Hyeun Wook; Lee, Young Choon; Kim, Cheorl Ho.
In: Journal of Molecular Medicine, Vol. 91, No. 2, 01.02.2013, p. 271-282.Research output: Contribution to journal › Article
TY - JOUR
T1 - CAPE suppresses VEGFR-2 activation, and tumor neovascularization and growth
AU - Chung, Tae Wook
AU - Kim, Seok Jo
AU - Choi, Hee Jung
AU - Kwak, Choong Hwan
AU - Song, Kwon Ho
AU - Suh, Seok Jong
AU - Kim, Keuk Jun
AU - Ha, Ki Tae
AU - Park, Young Guk
AU - Chang, Young Chae
AU - Chang, Hyeun Wook
AU - Lee, Young Choon
AU - Kim, Cheorl Ho
PY - 2013/2/1
Y1 - 2013/2/1
N2 - The growth and metastasis of human solid tumors and the development of conditions such as diabetic retinopathy, rheumatoid arthritis, inflammatory psoriasis, and others are regulated by the balance between angiogenic stimulators and inhibitors released in the angiogenic-pathological microenvironment. Vascular endothelial growth factor (VEGF), an angiogenic factor, is a potent endothelial-specific mitogen that activates endothelial cells in pathological angiogenesis. Recently, we demonstrated that caffeic acid phenethyl ester (CAPE) inhibits tumor growth, invasion, and metastasis. However, the precise molecular mechanism underlying the inhibitory effect of CAPE on VEGF-mediated angiogenesis remains unknown. Here, we show that CAPE suppressed VEGF-induced proliferation, tube formation, migration, the formation of actin stress fibers and loss of VE-cadherin at cell-cell contacts in endothelial cells, indicating the inhibition of VEGF-mediated VEGF receptor-2 (VEGFR-2) and its downstream signal activation in vitro. CAPE blocked VEGF-stimulated neovascularization in the Matrigel plugs assay, and reduced vascular permeability in mouse skin capillaries in vivo. CAPE inhibited the growth and neovascularization of primary tumor cells in C57BL/6 and BALB/c mice inoculated with Lewis lung carcinoma, colon carcinoma, and melanoma cells. These results suggest that CAPE negatively modulates VEGF-induced angiogenesis by suppressing VEGFR-2 activation, and might be a therapeutic avenue for anti-angiogenesis.
AB - The growth and metastasis of human solid tumors and the development of conditions such as diabetic retinopathy, rheumatoid arthritis, inflammatory psoriasis, and others are regulated by the balance between angiogenic stimulators and inhibitors released in the angiogenic-pathological microenvironment. Vascular endothelial growth factor (VEGF), an angiogenic factor, is a potent endothelial-specific mitogen that activates endothelial cells in pathological angiogenesis. Recently, we demonstrated that caffeic acid phenethyl ester (CAPE) inhibits tumor growth, invasion, and metastasis. However, the precise molecular mechanism underlying the inhibitory effect of CAPE on VEGF-mediated angiogenesis remains unknown. Here, we show that CAPE suppressed VEGF-induced proliferation, tube formation, migration, the formation of actin stress fibers and loss of VE-cadherin at cell-cell contacts in endothelial cells, indicating the inhibition of VEGF-mediated VEGF receptor-2 (VEGFR-2) and its downstream signal activation in vitro. CAPE blocked VEGF-stimulated neovascularization in the Matrigel plugs assay, and reduced vascular permeability in mouse skin capillaries in vivo. CAPE inhibited the growth and neovascularization of primary tumor cells in C57BL/6 and BALB/c mice inoculated with Lewis lung carcinoma, colon carcinoma, and melanoma cells. These results suggest that CAPE negatively modulates VEGF-induced angiogenesis by suppressing VEGFR-2 activation, and might be a therapeutic avenue for anti-angiogenesis.
KW - Angiogenesis
KW - Caffeic acid phenethyl ester (CAPE)
KW - Vascular endothelial growth factor (VEGF)
KW - Vascular endothelial growth factor receptor-2 (VEGFR-2)
UR - http://www.scopus.com/inward/record.url?scp=84873969414&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84873969414&partnerID=8YFLogxK
U2 - 10.1007/s00109-012-0952-6
DO - 10.1007/s00109-012-0952-6
M3 - Article
C2 - 22935775
AN - SCOPUS:84873969414
VL - 91
SP - 271
EP - 282
JO - Journal of Molecular Medicine
JF - Journal of Molecular Medicine
SN - 0946-2716
IS - 2
ER -