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

The FASEB Journal express article 10.1096/fj.01-0028fje. Published online June 8, 2001. [b]Suppression of angiogenesis, tumor growth,and wound healing by resveratrol, a natural compound in red wine and grapes[/b] Ebba Bråkenhielm,* Renhai Cao,* and Yihai Cao The first two authors contributed equally to this work. Corresponding author: Yihai Cao, M.D., Ph.D., Laboratory of Angiogenesis Research, Microbiology and Tumor Biology Center, Karolinska Institute, S-171 77 Stockholm, Sweden. Email: yihai.cao@mtc.ki.se [b]ABSTRACT[/b] Resveratrol (3,5,4'-trihydroxystilbene) is a natural compound found in several plants, including grapes, peanuts, and pines, and in their related products. Red wine is probably the most frequently consumed drink that is enriched in resveratrol. We investigated whether drinking resveratrol could suppress angiogenesis, a process of blood vessel growth involved in initiation, development, and progression of many diseases, including cancer, metastasis, and diabetic retinopathy. We found that resveratrol suppresses the growth of new blood vessels in animals. It directly inhibits capillary endothelial cell growth. It blocks both VEGF- and FGF-receptormediated angiogenic responses. In addition, resveratrol inhibits the phosphorylation of mitogenactivated kinase isoforms (MAPKp44/MAPKp42) induced by fibroblast growth factor-2 in proliferating endothelial cells in a dose-dependent manner. Oral administration of resveratrol significantly inhibits the growth of a murine fibrosarcoma in mice, and it significantly delays angiogenesis-dependent wound healing in mice. Our findings suggest that ingestion of resveratrol-enriched food could be beneficial for the prevention of cancer. However, its antiangiogenic effect could delay wound healing and possibly other angiogenesis-dependent processes under physiological conditions. Key words: resveratrol • red wine • cancer • angiogenesis • MAP kinase