Grape seed proanthocyanidins inhibit colon cancer-induced angiogenesis through suppressing the expression of VEGF and Ang1

• Published in: International journal of molecular medicine Vol. 30; no. 6; p. 1410
• Main Authors: Huang, Shuangsheng, Yang, Ninggang, Liu, Yuanyuan, Gao, Jing, Huang, Tao, Hu, Lamei, Zhao, Jin, Li, Yongquan, Li, Caili, Zhang, Xiaosu
• Format: Journal Article
• Language: English
• Published: Greece 01.12.2012
• Subjects: Angiogenesis Inhibitors - pharmacology; Angiogenesis Inhibitors - therapeutic use; Animals; Antineoplastic Agents, Phytogenic - pharmacology; Antineoplastic Agents, Phytogenic - therapeutic use; Cell Line, Tumor; Cell Movement; Cell Survival; Chick Embryo; Chorioallantoic Membrane - blood supply; Chorioallantoic Membrane - drug effects; Colonic Neoplasms - blood supply; Colonic Neoplasms - drug therapy; Culture Media, Conditioned; Grape Seed Extract - pharmacology; Grape Seed Extract - therapeutic use; Humans; Neovascularization, Pathologic - prevention & control; Proanthocyanidins - pharmacology; Proanthocyanidins - therapeutic use; Reactive Oxygen Species - metabolism; Ribonuclease, Pancreatic - metabolism; Vascular Endothelial Growth Factor A - metabolism; Xenograft Model Antitumor Assays
• ISSN: 1791-244X
• DOI: 10.3892/ijmm.2012.1147

Tumor cells trigger angiogenesis through overexpression of various angiogenic factors including vascular endothelial growth factor (VEGF) and angiopoietin 1 (Ang1). Therefore, inhibition of the expression of both VEGF and Ang1, the initial step of tumor angiogenesis, is a promising strategy for cancer chemoprevention and therapy. Grape seed proanthocyanidins (GSPs) are widely consumed dietary supplements that have antitumor activity. Due to their polymeric structure, GSPs are poorly absorbed along the gastrointestinal tract and can reach the colon at high concentrations, allowing these chemicals to act as chemopreventive agents for colon cancer. In the present study, we found that GSPs inhibited colon tumor-induced angiogenesis and, thus, the growth of colon tumor xenografts on the chick chorioallantoic membranes. The mechanisms of their action were related to inhibiting the expression of both VEGF and Ang1 through scavenging reactive oxygen species. Previous studies have demonstrated that the chemopreventive effects of GSPs on colon cancer are associated with their growth inhibitory and apoptosis-inducing effects. Our results demonstrate another mechanism by which GSPs inhibit colon tumor growth, which will be helpful for developing GSPs as a pharmacologically safe angiopreventive agent against colorectal cancer.