Anti-angiogenic activity of para-coumaric acid methyl ester on HUVECs in vitro and zebrafish in vivo
Autor: | Ping Wei, He-Zhong Zhang, Chong-Yong Li, Ming-Fang He, Rui-Xue Wang, Mei-Hui Liu, Jia-Qi Wu |
---|---|
Rok vydání: | 2018 |
Předmět: |
Vascular Endothelial Growth Factor A
0301 basic medicine Coumaric Acids Angiogenesis Pharmaceutical Science Angiogenesis Inhibitors Inflammation Umbilical vein Receptors TIE 03 medical and health sciences 0302 clinical medicine Cell Movement In vivo Drug Discovery Human Umbilical Vein Endothelial Cells medicine Animals Humans Zebrafish Cell Proliferation Pharmacology Tube formation Neovascularization Pathologic biology Chemistry Cell growth Zebrafish Proteins biology.organism_classification Vascular Endothelial Growth Factor Receptor-2 In vitro Cell biology 030104 developmental biology Complementary and alternative medicine 030220 oncology & carcinogenesis cardiovascular system Molecular Medicine medicine.symptom Signal Transduction |
Zdroj: | Phytomedicine. 48:10-20 |
ISSN: | 0944-7113 |
DOI: | 10.1016/j.phymed.2018.04.056 |
Popis: | Background Para-coumaric acid methyl ester (pCAME) is one of the bioactive components of Costus speciosus (Koen) Sm. (Zingiberaceae). This plant is traditionally used in Asia to treat catarrhal fevers, worms, dyspepsia, and skin diseases. Purpose To investigate the anti-angiogenic activity of pCAME and its molecular mechanism of action. Study design We investigated the anti-angiogenic activity of pCAME on human umbilical vein endothelial cells (HUVECs) in vitro and zebrafish (Danio rerio) in vivo. Methods In vitro cell proliferation, would healing, migration and tube formation assays were used, along with in vivo physiological angiogenic vessel formation, tumor-induced angiogenic vessel formation assays on zebrafish model. qRT-PCR and RNA-seq were also used for the target investigation. Results pCAME could inhibit the proliferation, would healing, migration and tube formation of HUVECs, disrupt the physiological formation of intersegmental vessels (ISVs) and the subintestinal vessels (SIVs) of zebrafish embryos, and inhibit tumor angiogenesis in the zebrafish cell-line derived xenograft (zCDX) model of SGC-7901 in a dose-dependent manner. Mechanistic studies revealed that pCAME inhibited vegf/vegfr2 and ang/tie signaling pathways in zebrafish by quantitative RT-PCR analysis, and regulated multi-signaling pathways involving immune, inflammation and angiogenesis in SGC-7901 zCDX model by RNA-seq analysis. Conclusion pCAME may be a multi-target anti-angiogenic drug candidate and hold great potential for developing novel therapeutic strategy for cancer treatment. |
Databáze: | OpenAIRE |
Externí odkaz: |