Epigallocatechin gallate inhibits HIF-1alpha degradation in prostate cancer cells.
Hypoxia-inducible factor-1, an alphabeta heterodimeric transcription factor, consists of a constitutively expressed HIF-1beta subunit and a hypoxia-inducible HIF-1alpha 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-1alpha expression in human prostate cancer cells. Surprisingly, we observed an EGCG-induced-dose-dependent increase in HIF-1-mediated transcription and HIF-1alpha 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-1alpha, thus preventing HIF-1alpha and pVHL interaction.
Thomas
Rusha
R
Department of Molecular Biology and Immunology, University of North Texas Health Science Center, Fort Worth, TX 76107-2699, USA.
Kim
Myoung H
MH
D002392:Catechin / Q000008:administration & dosage / Q000031:analogs & derivatives*; D045744:Cell Line, Tumor; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D051793:Hypoxia-Inducible Factor 1; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D008297:Male; D009687:Nuclear Proteins / Q000378:metabolism*; D011471:Prostatic Neoplasms / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism*; D015854:Up-Regulation / Q000187:drug effects
D004268:DNA-Binding Proteins; C497442:HIF1A protein, human; D051793:Hypoxia-Inducible Factor 1; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D009687:Nuclear Proteins; D014157:Transcription Factors; D002392:Catechin; C045651:epigallocatechin gallate