Consumption of tea has been shown to inhibit the growth of several tumour types in animals, including cancers of the lung and oesophagus1,2,3. Drinking tea, especially green tea, is also associated with a lower incidence of human cancer1. The mechanisms of cancer inhibition are not known, although several hypotheses have been proposed. We investigated whether drinking green tea could suppress angiogenesis, a process of blood-vessel growth required for tumour growth and metastasis. We find that green tea, and one of its components, epigallocatechin-3-gallate (EGCG), significantly prevents the growth of new blood vessels in animals. This finding indicates that drinking tea may be beneficial for the prevention and treatment of angiogenesis-dependent diseases, including cancer and blindness caused by diabetes.
EGCG has been reported to inhibit urokinase, which may be used by some tumours for the invasion of neighbouring healthy tissues4. However, the effective concentration of EGCG seems to be too high for it to be physiologically relevant for tea drinkers5. The growth of almost all types of tumour is dependent on angiogenesis, and the enlargement and metastasis of tumours is disrupted when this is suppressed6.
We thought that the inhibition of tumour growth by green tea might be mediated through the suppression of blood-vessel growth. To determine whether green tea could inhibit endothelial cell growth, we assayed EGCG on bovine capillary endothelial cells stimulated with the fibroblast growth factor FGF-2, as described7. We found that EGCG inhibited endothelial cell growth in a dose-dependent manner (Fig. 1a). The inhibition appeared to be specific to endothelial cells because non-endothelial cells, including murine T241 fibrosarcoma tumour cells, murine fibroblast cells, and rat smooth-muscle cells, were insensitive to EGCG treatment at the concentrations used.
We examined the effect of EGCG on angiogenesis in the chick chorioallantoic membrane assay8. Over a concentration range of 1 to 100 µg per disc, EGCG inhibited new blood-vessel growth in a dose-dependent manner (Fig. 1g), as measured by the formation of avascular zones.
To investigate whether tea could suppress angiogenesis, we made green tea the sole drinking fluid for mice and examined the effect of oral consumption on the inhibition of corneal neovascularization stimulated by vascular endothelial growth factor (VEGF). The corneal model is a rigorous antiangiogenic assay, requiring systemic administration of a putative angiogenesis inhibitor to suppress neovascularization induced by 160 ng of VEGF in the cornea. The amount of green tea in the drinking water was 1.25% (4.69 mg ml-1) containing 708 µg ml-1 EGCG9,10. The concentration of EGCG in the plasma was previously reported to be in the range of 0.1-0.3 µM, which is similar to levels in humans after drinking two or three cups of tea11.
This tea preparation has been shown to significantly suppress the growth and progression of tumours in the lungs in animal models9. Compared with the control group that drank water alone (Fig. 1b), drinking tea significantly prevented VEGF-induced corneal neovascularization (Fig. 1c). Blood-vessel length (Fig. 1d), clock-hours of corneal neovascularization (the proportion of the circumference that is vascularized if the eye is viewed as a clock; Fig. 1e) and area of neovascularization (Fig. 1f) in seven corneas from four mice in the tea-drinking group were inhibited by approximately 55, 35 and 70%, respectively.
Our data indicate that EGCG suppresses endothelial cell growth in vitro and the formation of new blood vessels in chick chorioallantoic membrane. Drinking green tea significantly prevents corneal neovascularization induced by one of the most potent angiogenic factors, VEGF. Because the growth of all solid tumours is dependent on angiogenesis6, this finding may explain why drinking green tea prevents the growth of a variety of different types of tumour.
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Cao, Y., Cao, R. Angiogenesis inhibited by drinking tea. Nature 398, 381 (1999). https://doi.org/10.1038/18793
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