The DOI matches its Crossref record; 44 of the 44 references it cites were found in a registry or an index.
A prodrug of green tea polyphenol (–)-epigallocatechin-3-gallate (Pro-EGCG) serves as a novel angiogenesis inhibitor in endometrial cancer
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.
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“Numerous studies, both in vitro using various cancer cell lines and in vivo in animal models, have consistently demonstrated the ability of EGCG to inhibit the initiation, promotion, and progression of different types of tumors.141–145”
From Drug repurposing for cancer therapy (2024) · cites this paper as [144]
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Metadata
- Authors
- Wang, J., Man, G. C. W., Chan, T. H., Kwong, J., & Wang, C. C.
- Affiliations
- Chinese University of Hong Kong (HK)
- Hong Kong Polytechnic University (HK)
- Corresponding author
- Wang, Chi Chiu
- Venue
- Cancer Letters
- Publisher
- Elsevier BV
- Published
- 2018-01
- Volume
- 412
- Pages
- 10-20
- ISSN
- 0304-3835 (ISSN-L)
- OpenAlex
- W2761665465
- Cited by
- 127
- References
- 44
- Citations by year
- 2026: 6 · 2025: 11 · 2024: 16 · 2023: 11 · 2022: 12 · 2021: 18 · 2020: 29 · 2019: 13 · 2018: 11
- FWCI
- 5.92
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Cancer Letters (publishedVersion)
- PubMed (publishedVersion)
- PolyU Institutional Research Archive (Hong Kong Polytechnic University) (submittedVersion)
- Funders
- University of Hong Kong
- Chinese University of Hong Kong
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Angiogenesis and VEGF in Cancer
- Life Sciences › Agricultural and Biological Sciences › Food Science › Tea Polyphenols and Effects
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
- Keywords
- epigallocatechin gallate, green tea polyphenols, prodrugs, endometrial cancer, tumor angiogenesis, anti-angiogenic therapy, VEGF-A, HIF-1α, PI3K/AKT/mTOR pathway, CXCL12, tumor-associated macrophages, macrophage infiltration, tumor stroma, xenograft models
- MeSH terms
- Phosphoinositide-3 Kinase Inhibitors, Animals, Catechin, Cell Movement, Female, Humans, Macrophages, Prodrugs, Tea, Endometrial Neoplasms, Angiogenesis Inhibitors, Vascular Endothelial Growth Factor A, Mice, Chemokine CXCL12
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