Drug Design, Development and Therapy (Sep 2018)
Murrangatin suppresses angiogenesis induced by tumor cell–derived media and inhibits AKT activation in zebrafish and endothelial cells
Abstract
Weiqing Long,1,* Mingjun Wang,2,* Xiongming Luo,3 Guixian Huang,4 Jianwen Chen5 1Department of Clinical Laboratory, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China; 2Department of Pharmacy, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China; 3CAS Key Laboratory of Tropical Marine Bio-resources and Ecology, South China Sea Institute of Oceanology, Chinese Academy of Sciences, Guangzhou 510301, China; 4Department of Emergency, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China; 5School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China *These authors contributed equally to this work Introduction: Lung cancer is a major cancer type and a leading cause of cancer-related death. Angiogenesis plays a crucial role in lung cancer pathogenesis and its inhibition is beneficial to patients. Materials and methods: Murrangatin, a natural product, can inhibit the proliferation of lung cancer cells, so herein we investigated its anti-angiogenic effects in transgenic zebrafish TG (fli1: EGFP) and in lung cancer cell-induced angiogenesis in human umbilical vein endothelial cells. Results: We found that murrangatin strongly inhibited the growth of subintestinal vessels in zebrafish embryos and tumor conditioned media-induced angiogenic phenotypes including cell proliferation, cell invasion, cell migration, and tube formation. Additionally, murrangatin greatly attenuated conditioned medium-induced AKT phosphorylation, but not extracellular signal-regulated kinase 1/2 phosphorylation. Discussion and conclusion: These findings indicate that murrangatin can inhibit tumor-induced angiogensis, at least in part through the regulation of AKT signaling pathways. Murrangatin may, therefore, be a potential candidate for the development of new anti-lung-cancer drugs. Keywords: anti-angiogenesis, murrangatin, conditioned medium, zebrafish, HUVECs, AKT
