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Abstract Title:

A prodrug of green tea polyphenol (-)-epigallocatechin-3-gallate (Pro-EGCG) serves as a novel angiogenesis inhibitor in endometrial cancer.

Abstract Source:

Cancer Lett. 2017 Oct 9. Epub 2017 Oct 9. PMID: 29024813

Abstract Author(s):

Jianzhang Wang, Gene Chi Wai Man, Tak Hang Chan, Joseph Kwong, Chi Chiu Wang

Article Affiliation:

Jianzhang Wang

Abstract:

Anti-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.

Study Type : In Vitro Study

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