Triphenylethylene-Coumarin Hybrid TCH-5c Suppresses Tumorigenic Progression in Breast Cancer Mainly Through the Inhibition of Angiogenesis

Author(s):

Naipeng Cui, Dan-Dan Lin, Yang Shen, Jian-Guo Shi, Bing Wang, Ming-Zhi Zhao, Lishuang Zheng, Hua Chen* and Jian-Hong Shi*   Pages 1253 - 1261 ( 9 )

Abstract:

<P>Background: Coumarins are a wide group of naturally occurring compounds which exhibit a wide range of biological properties such as anti-cancer activities. Here, we characterized the biological functions of three Triphenylethylene-Coumarin Hybrids (TCHs) both in cell culture and nude mouse model. </P><P> Methods: Cell proliferation assay was performed in the cell cultures of both EA.hy926 endothelial cell and breast cancer cell lines treated with different concentrations of compound TCH-10b, TCH-5a and TCH-5c. Flowcytometry assay and Western blotting were used to further investigate the effect and mechanism of TCH-5c on EA.hy926 cell proliferation and cell cycle. The effects of TCH-5c on endothelial cell migration and angiogenesis were determined using cytoskeleton staining, migration assay and tube formation assay. Inhibition of breast cancer cell line derived VEGF by TCH-5c was shown through ELISA and the use of conditioned media. SK-BR-3 xenograft mouse model was established to further study the anti-tumorigenic role of compound TCH-5c in vivo. </P><P> Results: We found that compound TCH-5c has inhibitory effects on both vascular endothelial cells and breast cancer cell lines. Compound TCH-5c inhibited proliferation, resulted in cell death, increased p21 protein expression to induce G0/G1 arrest and changed endothelial cell cytoskeleton organization and migration in EA.hy926 endothelial cells. Compound TCH-5c also inhibited breast cancer cell line derived VEGF secretion, decreased breast cancer cell-induced endothelial cell tube formation in vitro and suppressed SK-BR-3 breast cancer cell-initiated tumor formation in vivo. </P><P> Conclusion: Our study demonstrates that the coumarin derivative TCH-5c exerts its anti-cancer effects by 1. inhibiting endothelial cell proliferation, migration. 2. suppressing tube formation and angiogenesis induced by breast cancer cells in vitro and in vivo. Our results have potential implications in developing new approaches against breast cancer.</P>

Keywords:

Breast neoplasms, angiogenesis inhibitors, vascular endothelial growth factor, coumarin, TCH-5c, western blotting.

Affiliation:

Department of Breast Surgery, Affiliated Hospital of Hebei University, Baoding 071000, Central Laboratory, Hebei Key Laboratory of Cancer Radiotherapy and Chemotherapy, Affiliated Hospital of Hebei University and Medical College of Hebei University, Baoding 071000, Central Laboratory, Hebei Key Laboratory of Cancer Radiotherapy and Chemotherapy, Affiliated Hospital of Hebei University and Medical College of Hebei University, Baoding 071000, Department of Urinary Surgery, Chinese People&#39;s Liberation Army No.252 Hospital, Baoding 071000, Central Laboratory, Hebei Key Laboratory of Cancer Radiotherapy and Chemotherapy, Affiliated Hospital of Hebei University and Medical College of Hebei University, Baoding 071000, Central Laboratory, Hebei Key Laboratory of Cancer Radiotherapy and Chemotherapy, Affiliated Hospital of Hebei University and Medical College of Hebei University, Baoding 071000, Central Laboratory, Hebei Key Laboratory of Cancer Radiotherapy and Chemotherapy, Affiliated Hospital of Hebei University and Medical College of Hebei University, Baoding 071000, Key Laboratory of Chemical Biology of Hebei Province, College of Chemistry and Environmental Science, Hebei University, Baoding 071000, Central Laboratory, Hebei Key Laboratory of Cancer Radiotherapy and Chemotherapy, Affiliated Hospital of Hebei University and Medical College of Hebei University, Baoding 071000

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