We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Xanthorrhizol Suppresses Vascular Endothelial Growth Factor-Induced Angiogenesis by Modulating Akt/eNOS Signaling and the NF-κB-Dependent Expression of Cell Adhesion Molecules.
- Authors
Lee, Sun Kyoung; Kim, Mi-Jeong; Son, Seung Hwa; Kim, Ki Rim; Park, Kwang-Kyun; Chung, Won-Yoon
- Abstract
Angiogenesis plays a crucial role in tumor growth and metastasis. Vascular endothelial growth factor (VEGF)-stimulated endothelial cell proliferation and migration are critical steps in tumor angiogenesis. Here, we investigated the anti-angiogenic activity of xanthorrhizol, a sesquiterpenoid isolated from the Indonesian medicinal plant Curcuma xanthorrhiza. Xanthorrhizol at noncytotoxic concentrations inhibited the proliferation, migration, and formation of capillary-like tubes in VEGF-treated human umbilical vein endothelial cells (HUVECs). Xanthorrhizol inhibited the phosphorylation of Akt and endothelial nitric oxide synthase (eNOS) and the expression of vascular cell adhesion molecule (VCAM)-1 and E-selectin in VEGF-treated HUVECs. The expression and transcriptional activity of NF- κ B were downregulated by xanthorrhizol in VEGF-treated HUVECs. Furthermore, xanthorrhizol significantly inhibited VEGF-induced angiogenesis in the chorioallantoic membrane of fertilized eggs and Matrigel plugs subcutaneously injected into mice. Xanthorrhizol inhibited tumor volume and tumor-derived angiogenesis in mice inoculated with breast cancer cells. The in vitro and in vivo anti-angiogenic activities of xanthorrhizol were as potent as those of curcumin, a well-known anticancer agent derived from C. longa. Taken together, xanthorrhizol inhibits VEGF-induced angiogenesis of endothelial cells by blocking the activation of the PI3K/Akt/eNOS axis and subsequent upregulation of adhesion molecules induced by the transcriptional activation of NF- κ B. Xanthorrhizol is a promising anti-angiogenic agent and can serve as a beneficial agent to enhance anticancer treatments.
- Subjects
IN vitro studies; MEDICINAL plants; NEOVASCULARIZATION inhibitors; TERPENES; NITRIC-oxide synthases; IN vivo studies; XENOGRAFTS; ANALYSIS of variance; ANIMAL experimentation; WESTERN immunoblotting; CELLULAR signal transduction; T-test (Statistics); PATHOLOGIC neovascularization; DNA-binding proteins; CELL adhesion molecules; DESCRIPTIVE statistics; RESEARCH funding; VASCULAR endothelial growth factors; OXIDOREDUCTASES; MOLECULAR structure; DATA analysis software; MICE; PHOSPHORYLATION; PHARMACODYNAMICS
- Publication
American Journal of Chinese Medicine, 2021, Vol 49, Issue 3, p737
- ISSN
0192-415X
- Publication type
Article
- DOI
10.1142/S0192415X21500348