A prodrug of green tea polyphenol (–)-epigallocatechin-3-gallate (Pro-EGCG) serves as a novel angiogenesis inhibitor in endometrial cancer
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AbstractAnti-angiogenesis effect of a prodrug of green tea polyphenol (–)-epigallocatechin-3-gallate (Pro-EGCG) in malignant tumors is not well studied. Here, we investigated how the treatment with Pro-EGCG inhibited tumor angiogenesis in endometrial cancer. Tumor xenografts of human endometrial cancer were established and subjected to microarray analysis after Pro-EGCG treatment. First, we showed Pro-EGCG inhibited tumor angiogenesis in xenograft models through down-regulation of vascular endothelial growth factor A (VEGFA) and hypoxia inducible factor 1 alpha (HIF1α) in tumor cells and chemokine (C-X-C motif) ligand 12 (CXCL12) in host stroma by immunohistochemical staining. Next, we investigated how HIF1α/VEGFA was down-regulated and how the reduction of CXCL12 inhibited tumor angiogenesis. We found that VEGFA secretion from endometrial cancer cells was decreased by Pro-EGCG treatment through inhibiting PI3K/AKT/mTOR/HIF1α pathway. Furthermore, the down-regulation of CXCL12 in stromal cells by Pro-EGCG treatment restricted migration and differentiation of macrophages thereby inhibited infiltration of VEGFA-expressing tumor-associated macrophages (TAMs). Taken together, we demonstrated that treatment with Pro-EGCG not only decreases cancer cell-secreted VEGFA but also inhibits TAM-secreted VEGFA in endometrial cancer. These findings demonstrate that Pro-EGCG is a novel angiogenesis inhibitor for endometrial cancer.
Acceptance Date29/09/2017
All Author(s) ListWang Jianzhang, Man Gene Chi Wai, Chan Tak Hang, Kwong Joseph, Wang Chi Chiu
Journal nameCancer Letters
Volume Number412
PublisherElsevier Ireland Ltd
Place of PublicationNetherlands
Pages10 - 20
LanguagesEnglish-United States
KeywordsPro-EGCG, Endometrial cancer, Angiogenesis, Hypoxia inducible factor 1 alpha, Tumor-associated macrophages

Last updated on 2020-19-09 at 03:03