Flavonoids apigenin and quercetin inhibit melanoma growth and metastatic potential

Flavonoids are a class of polyphenolic compounds widely distributed in the plant kingdom, which display a variety of biological activities, including chemoprevention and tumor growth inhibition. Our aim was to investigate the effects of several polyphenols on the growth and metastatic potential of B 16-BL6 melanoma cells in vivo. Intraperitoneal administration of quercetin, apigenin, (-)-epigallocathechin-3-gallate (EGCG), resveratrol, and the ant i-estrogen tamoxifen, at the time of i.m. injection of B16-BL6 cells into s yngeneic mice, resulted in a significant, dose-dependent delay of tumor gro wth, without toxicity. The relative descending order of potency was EGCG > apigenin = quercetin = tamoxifen > resveratrol > control. Furthermore, poly phenols significantly potentiated the inhibitory effect of a non-toxic dose of cisplatin. When tested for the ability to inhibit lung colonization, qu ercetin, apigenin, and tamoxifen (but not EGCG or resveratrol) significantl y decreased the number of B16-BL6 colonies in the lungs in a dose-dependent manner, with quercetin and apigenin being more effective than tamoxifen. I nterestingly, quercetin, apigenin, and tamoxifen (but not EGCG or resveratr ol) significantly decreased the invasion of B16-BL6 cells in vitro, with qu ercetin and apigenin being more effective than tamoxifen. This suggests tha t anti-invasive activity is one of the mechanisms underlying inhibition of lung colonization by quercetin and apigenin. In conclusion, quercetin and a pigenin inhibit melanoma growth and invasive and metastatic potential; ther efore, they may constitute a valuable tool in the combination therapy of me tastatic melanoma. Int. J. Cancer 87:595-600, 2000. (C) 2000 Wiley-Liss, In c.