Epigallocatechin gallate inhibits HIF-1α degradation in prostate cancer cells

Hypoxia-inducible factor-1, an alpha beta heterodimeric transcription factor, consists of a constitutively expressed HIF-1 beta subunit and a hypoxia-inducible HIF-1 alpha subunit, and contributes to hypoxia-mediated tumor angiogenesis. Numerous epidemiologic and laboratory studies indicate that green tea has cancer preventive activity which has been attributed to its polyphenol components, the major one being epigallocatechin gallate (EGCG). This study investigated the effect of EGCG on normoxic HIF-1 alpha expression in human prostate cancer cells. Surprisingly, we observed an EGCG-induced-dose-dependent increase in HIF-1-mediated transcription and HIF-1 alpha protein levels under normoxia. However, concomitant treatment of the prostate cancer cells with EGCG and ferrous ions abolished the increase in HIF-1-mediated transcription that was seen with EGCG treatment alone, suggesting that EGCG may act as a ferrous ion chelator. Furthermore, we determined, for the first time, that EGCG inhibits prolyl hydroxylation of HIF-1 alpha, thus preventing HIF-1 alpha and pVHL interaction. (c) 2005 Elsevier Inc. All rights reserved.