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

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

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.

Citation

Wang, J., Man, G. C. W., Chan, T. H., Kwong, J., & Wang, C. C. (2018). A prodrug of green tea polyphenol (–)-epigallocatechin-3-gallate (Pro-EGCG) serves as a novel angiogenesis inhibitor in endometrial cancer. Cancer Letters, 412, 10-20. https://doi.org/10.1016/j.canlet.2017.09.054

• Journal Article Type: Article
• Acceptance Date: Sep 29, 2017
• Online Publication Date: Oct 9, 2017
• Publication Date: Jan 1, 2018
• Deposit Date: Jun 20, 2023
• Journal: Cancer Letters
• Print ISSN: 0304-3835
• Publisher: Elsevier
• Peer Reviewed: Peer Reviewed
• Volume: 412
• Pages: 10-20
• DOI: https://doi.org/10.1016/j.canlet.2017.09.054
• Keywords: Cancer Research; Oncology
• Additional Information: This article is maintained by: Elsevier; Article Title: A prodrug of green tea polyphenol (–)-epigallocatechin-3-gallate (Pro-EGCG) serves as a novel angiogenesis inhibitor in endometrial cancer; Journal Title: Cancer Letters; CrossRef DOI link to publisher maintained version: https://doi.org/10.1016/j.canlet.2017.09.054; Content Type: article; Copyright: © 2017 Elsevier B.V. All rights reserved.