Suppression of angiogenesis, tumor growth, and wound healing by resveratrol, a natural compound in red wine and grapes

Resveratrol (3,5,4'-trihydroxystilbene) is a natural compound found in seve ral plants, including grapes, peanuts, and pines, and in their related prod ucts. Red wine is probably the most frequently consumed drink that is enric hed in resveratrol. We investigated whether drinking resveratrol could supp ress angiogenesis, a process of blood vessel growth involved in initiation, development, and progression of many diseases, including cancer, metastasi s, and diabetic retinopathy. We found that resveratrol suppresses the growt h of new blood vessels in animals. It directly inhibits capillary endotheli al cell growth. It blocks both VEGF- and FGF-receptor-mediated angiogenic r esponses. In addition, resveratrol inhibits the phosphorylation of mitogen- activated kinase isoforms (MAPK(p44)/MAPK(p42)) induced by fibroblast growt h factor-2 in proliferating endothelial cells in a dose-dependent manner. O ral administration of resveratrol significantly inhibits the growth of a mu rine fibrosarcoma in mice, and it significantly delays angiogenesis-depende nt wound healing in mice. Our findings suggest that ingestion of resveratro l-enriched food could be beneficial for the prevention of cancer. However, its antiangiogenic effect could delay wound healing and possibly other angi ogenesis-dependent processes under physiological conditions.