Anti-Angiogenesis Efficacy of the Garlic Ingredient Alliin and Antioxidants: Role of Nitric Oxide and p53

Abstract

Abstract: Alliin, a compound derived from garlic, demonstrated dose-dependent inhibition of fibroblast growth factor-2 (FGF2)-induced human endothelial cell (EC) tube formation and angiogenesis in the chick chorioallantoic membrane (CAM) model. Additionally, alliin demonstrated potent inhibition of vascular endothelial growth factor (VEGF)-induced angiogenesis in the CAM model. The antioxidant vitamins C and E significantly (P < 0.001) enhanced the inhibitory efficacy of alliin on FGF2-induced EC tube formation and angiogenesis. Alliin significantly increased (P < 0.01) nitric oxide (NO) release into the CAM fluid, which was further enhanced by vitamins C and E. The NO synthesis inhibitor nitro-L-arginine methyl ester (L-NAME) reversed the anti-angiogenesis efficacy of alliin in the CAM model. Vitamins C and E significantly enhanced the anticancer efficacy of alliin in inhibiting colon and fibrosarcoma tumor growth. Alliin significantly inhibited both FGF2 and VEGF secretion from human fibrosarcoma cells in a concentration-dependent manner. Additionally, alliin up-regulated the p53 production in FGF2-stimulated EC. These data indicated a synergistic effect of antioxidants on the anti-angiogenesis and anticancer efficacy of alliin. These data also suggest the implication of cellular NO and p53 as mediators of anti-angiogenesis and anticancer effects of alliin.