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Epidemiological studies have shown that a diet rich in fruits and vegetables has a beneficial preventive effect on cardiovascular diseases and cancer by mechanisms that have not yet been elucidated. In this work, we investigated the antiangiogenic activities of anthocyanidins, a class of polyphenols present at high levels in fruits. Among the tested anthocyanidins (cyanidin, delphinidin, malvidin, pelargonidin, peonidin and petunidin), delphinidin was the most potent angiogenic inhibitor. In vitro, low concentrations of delphinidin inhibited vascular endothelial growth factor (VEGF)-induced tyrosine phosphorylation of VEGF receptor (VEGFR)-2, leading to the inhibition of downstream signaling triggered by VEGFR-2. Inhibition of VEGFR-2 by delphinidin inhibited the VEGF-induced activation of ERK-1/2 signaling and the chemotactic motility of human EC as well as their differentiation into capillary-like tubular structures in Matrigel and within fibrin gels. In vivo, delphinidin was able to suppress basic fibroblast growth factor-induced vessel formation in the mouse Matrigel plug assay. The identification of delphinidin as a naturally occurring inhibitor of VEGF receptors suggests that this molecule possesses important antiangiogenic properties that may be helpful for the prevention and treatment of cancer.

The concept of cancer prevention by use of naturally occuring substances that could be included in the diet is under investigation as a practical approach towards reducing cancer incidence, and therefore the mortality and morbidity associated with this disease. Tea, which is the most popularly consumed beverage aside from water, has been particularly associated with decreased risk of various proliferative diseases such as cancer and atherosclerosis in humans. Various studies have provided evidence that polyphenols are the strongest biologically active agents in green tea. Green tea polyphenols (GTPs) mainly consist of catechins (3-flavanols), of which (-)-epigallocatechin gallate is the most abundant and the most extensively studied. Recent observations have raised the possibility that green tea catechins, in addition to their antioxidative properties, also affect the molecular mechanisms involved in angiogenesis, extracellular matrix degradation, regulation of cell death and multidrug resistance. This article will review the effects and the biological activities of green tea catechins in relation to these mechanisms, each of which plays a crucial role in the development of cancer in humans. The extraction of polyphenols from green tea, as well as their bioavailability, are also discussed since these two important parameters affect blood and tissue levels of the GTPs and consequently their biological activities. In addition, general perspectives on the application of dietary GTPs as novel antiangiogenic and antitumor compounds are also presented.