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

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.

Anticancer and anti-angiogenesis effect of the leaf extract of <i>Sargassum wightii</i> against osteosarcoma cancer cells

“…These reports are in line with the present research findings. Similar results have been reported previously where allinin from garlic displayed significant inhibitory effect on fibroblast growth factor-2 (FGF-2)-induced tube formation and CAM angiogenesis (Mousa et al, 2005). Hence, it may be said that the anti-angiogenic activity of S. wightii might be correspond to the phytochemicals such as phenolics and flavonoids present in large amount in the ethanolic leaf extract of S. wightii.…”

Aged garlic extract restores nitric oxide bioavailability in cultured human endothelial cells even under conditions of homocysteine elevation

“…Cardiovascular effects of AGE are thought to be at least partly due to its antioxidant and thiol modifying properties (Ide and Lau, 2001;Lau, 2001;Mousa and Mousa, 2005). More recently, AGE has been reported to improve endothelial function and retard the progression of coronary calcifications in patients with coronary artery disease, who are already treated with statins (Budoff et al, 2004(Budoff et al, , 2009.…”

197. Highly Active Antiretroviral Therapy Drugs Inhibit In Vitro Cholesterol Efflux from Human Macrophage-Derived Foam Cells

“…We have chosen the concentration of 10 µM for all antioxidants because the affectivity of these compounds is readily comparable. 4,[32][33][34][35] Comparing the therapeutic magnitude of each agent may enhance our knowledge of these agents for the applications of reducing the complications of HAART drugs. In accordance with the current study, our previous studies also showed protective effects of Rb1 on ritonavir-induced inhibition in cholesterol efflux.4 Despite the antioxidant properties of vitamins E and C, their efficacy remains controversial in some recent clinical trials and meta-analyses.…”