A prodrug of green tea polyphenol (–)-epigallocatechin-3-gallate (Pro-EGCG) serves as a novel angiogenesis inhibitor in endometrial cancer
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...
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Published in | Cancer letters Vol. 412; pp. 10 - 20 |
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Main Authors | , , , , |
Format | Journal Article |
Language | English |
Published |
Ireland
Elsevier B.V
01.01.2018
Elsevier Limited |
Subjects | |
Online Access | Get full text |
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Summary: | 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.
•Pro-EGCG serves as a novel angiogenesis inhibitor in endometrial cancer.•Pro-EGCG reduces cancer cell-secreted VEGFA by inhibiting PI3K/AKT/mTOR/HIF1α pathway.•Pro-EGCG decreases TAM-secreted VEGFA by inhibiting infiltration of TAMs.•Pro-EGCG inhibits CXCL12-induced migration and differentiation of macrophages. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 0304-3835 1872-7980 |
DOI: | 10.1016/j.canlet.2017.09.054 |