EGCG and Its Role in Prostate Cancer Angiogenesis

Thomas, Rusha
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Thomas, Rusha, EGCG and its role in prostate cancer angiogenesis. Master of Science (Biochemistry and Molecular Biology), May 2005, 47 pages, 14 illustrations, reference list, 44 titles. Hypoxia inducible factor-1 (HIF-1)-mediated upregulation of vascular endothelial growth factor (VEGF) has been implicated in angiogenesis associated with malignancies. HIF-1 consists of a constitutively expressed HIF-1β subunit, and a hypoxia-inducible HIF-1α subunit. Hypoxic induction of HIF-1α correlates with increased transcriptional activation of its downstream target genes, including VEGF. 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 VEGF expression in PC-3ML human prostate cancer cells. In contrast to previous studies where EGCG inhibited VEGF expression in breast and colon cancer cell lines, our results demonstrated that EGCG has the ability to upregulate HIF-1α transcription factor via inhibition of prolyl hydroxylation and subsequent von Hippel-Lindau protein interaction. HIF-1α upregulation by EGCG led to increased VEGF promoter activity and protein expression.