Murrangatin suppresses angiogenesis induced by tumor cell-derived media and inhibits AKT activation in zebrafish and endothelial cells

• Published in: Drug design, development and therapy development and therapy, 2018-01, Vol.12, p.3107-3115
• Main Authors: Long, Weiqing, Wang, Mingjun, Luo, Xiongming, Huang, Guixian, Chen, Jianwen
• Format: Article
• Language: English
• Subjects: AKT; AKT protein; Angiogenesis; Angiogenesis Inhibitors - chemistry; Angiogenesis Inhibitors - isolation & purification; Angiogenesis Inhibitors - pharmacology; Animal genetic engineering; Animals; Anti-angiogenesis; Antiangiogenics; Backup software; Biological Products - chemistry; Biological Products - isolation & purification; Biological Products - pharmacology; Blood vessels; Cancer; Cancer cells; Cancer prevention; Cancer therapies; Cell migration; Cell Movement - drug effects; Cell proliferation; Cell Proliferation - drug effects; Cell Survival - drug effects; Cells, Cultured; Chemotherapy; Chromatography; Conditioned Medium; Conditioning; Coumarins - chemistry; Coumarins - isolation & purification; Coumarins - pharmacology; Culture Media, Conditioned - chemistry; Culture Media, Conditioned - pharmacology; Cytokines; Cytotoxicity; Danio rerio; Death; Drug development; Drug Screening Assays, Antitumor; Embryos; Endothelial cells; Endothelium; Extracellular signal-regulated kinase; Genetic engineering; Health aspects; Hospitals; Human Umbilical Vein Endothelial Cells - drug effects; Human Umbilical Vein Endothelial Cells - metabolism; Humans; HUVECs; Kinases; Laboratories; Lung cancer; Lung Neoplasms - drug therapy; Lung Neoplasms - metabolism; Lung Neoplasms - pathology; Metastasis; Molecular Conformation; Murrangatin; Natural products; Neovascularization, Pathologic - drug therapy; Neovascularization, Pathologic - metabolism; Neovascularization, Pathologic - pathology; Original Research; Pathogenesis; Phenotypes; Phosphorylation; Protein Kinase Inhibitors - chemistry; Protein Kinase Inhibitors - isolation & purification; Protein Kinase Inhibitors - pharmacology; Proto-Oncogene Proteins c-akt - antagonists & inhibitors; Proto-Oncogene Proteins c-akt - metabolism; Signal Transduction - drug effects; Structure-Activity Relationship; Tumors; Umbilical vein; Zebrafish; Zebrafish - embryology
• ISSN: 1177-8881; 1177-8881
• DOI: 10.2147/DDDT.S145956

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. 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. 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. 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.