Open AccessTriphenylethylene-Coumarin Hybrid TCH-5c Suppresses Tumorigenic Progression in Breast Cancer Mainly Through the Inhibition of Angiogenesis
Author(s) -
Naipeng Cui,
Dandan Lin,
Yang Shen,
Jianguo Shi,
Bing Wang,
Mingzhi Zhao,
Lishuang Zheng,
Hua Chen,
Jing Shi
Publication year - 2019
Publication title -
anti-cancer agents in medicinal chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.508
H-Index - 96
eISSN - 1875-5992
pISSN - 1871-5206
DOI - 10.2174/1871520619666190404155230
Subject(s) - angiogenesis , endothelial stem cell , cell growth , chemistry , cancer research , cell , cell culture , cancer cell , cancer , microbiology and biotechnology , biology , in vitro , medicine , biochemistry , genetics
Background: Coumarins are a wide group of naturally occurring compounds which exhibit a wide rangeof biological properties such as anti-cancer activities. Here, we characterized the biological functions of threeTriphenylethylene-Coumarin Hybrids (TCHs) both in cell culture and nude mouse model. Methods: Cell proliferation assay was performed in the cell cultures of both EA.hy926 endothelial cell and breastcancer cell lines treated with different concentrations of compound TCH-10b, TCH-5a and TCH-5c. Flowcytometryassay and Western blotting were used to further investigate the effect and mechanism of TCH-5c on EA.hy926cell proliferation and cell cycle. The effects of TCH-5c on endothelial cell migration and angiogenesis were determinedusing cytoskeleton staining, migration assay and tube formation assay. Inhibition of breast cancer cell linederived VEGF by TCH-5c was shown through ELISA and the use of conditioned media. SK-BR-3 xenograft mousemodel was established to further study the anti-tumorigenic role of compound TCH-5c in vivo. Results: We found that compound TCH-5c has inhibitory effects on both vascular endothelial cells and breast cancercell lines. Compound TCH-5c inhibited proliferation, resulted in cell death, increased p21 protein expression toinduce G0/G1 arrest and changed endothelial cell cytoskeleton organization and migration in EA.hy926 endothelialcells. Compound TCH-5c also inhibited breast cancer cell line derived VEGF secretion, decreased breast cancercell-induced endothelial cell tube formation in vitro and suppressed SK-BR-3 breast cancer cell-initiated tumorformation in vivo. Conclusion: Our study demonstrates that the coumarin derivative TCH-5c exerts its anti-cancer effects by 1. inhibitingendothelial cell proliferation, migration. 2. suppressing tube formation and angiogenesis induced by breastcancer cells in vitro and in vivo. Our results have potential implications in developing new approaches against breastcancer.