The coffee diterpene kahweol inhibits metastasis by modulating expressions of MMPs and VEGF via STAT3 inactivation

초록

Kahweol, a coffee-specific diterpene, is reported to have anti-cancer properties, although its precise chemopreventive mechanism remains unclear. The aim of our study was to determine the effect of kahweol on anti-metastatic activities and the possible mechanisms. Kahweol inhibited the migration and invasion ability of various cancer cells in vitro and decreased the secretion of metalloproteinase (MMP)-2, MMP-9, and VEGF in cancer cells via suppression of STAT3 activation. Kahweol also exhibited an inhibitory effect on lung metastasis in the experimental B16-F10 melanoma metastasis model. Moreover, kahweol inhibited migration and tube formation of endothelial cells in vitro, decreased the secretion of VEGF, and suppressed neovascularisation in Matrigel plugs in mice. Our findings demonstrate that kahweol inhibits metastasis through the disruption of STAT3-mediated transcription of the MMP and VEGF genes. (C) 2012 Elsevier Ltd. All rights reserved.

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