PUBLICATION
Murrangatin suppresses angiogenesis induced by tumor cell-derived media and inhibits AKT activation in zebrafish and endothelial cells
- Authors
- Long, W., Wang, M., Luo, X., Huang, G., Chen, J.
- ID
- ZDB-PUB-181006-3
- Date
- 2018
- Source
- Drug design, development and therapy 12: 3107-3115 (Journal)
- Registered Authors
- Keywords
- AKT, HUVECs, anti-angiogenesis, conditioned medium, murrangatin, zebrafish
- MeSH Terms
-
- Angiogenesis Inhibitors/chemistry
- Angiogenesis Inhibitors/isolation & purification
- Angiogenesis Inhibitors/pharmacology*
- Animals
- Biological Products/chemistry
- Biological Products/isolation & purification
- Biological Products/pharmacology
- Cell Movement/drug effects
- Cell Proliferation/drug effects
- Cell Survival/drug effects
- Cells, Cultured
- Coumarins/chemistry
- Coumarins/isolation & purification
- Coumarins/pharmacology*
- Culture Media, Conditioned/chemistry
- Culture Media, Conditioned/pharmacology
- Drug Screening Assays, Antitumor
- Human Umbilical Vein Endothelial Cells/drug effects*
- Human Umbilical Vein Endothelial Cells/metabolism
- Humans
- Lung Neoplasms/drug therapy*
- Lung Neoplasms/metabolism
- Lung Neoplasms/pathology
- Molecular Conformation
- Neovascularization, Pathologic/drug therapy*
- Neovascularization, Pathologic/metabolism
- Neovascularization, Pathologic/pathology
- 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
- Zebrafish/embryology
- PubMed
- 30288018 Full text @ Drug Des Devel Ther
Citation
Long, W., Wang, M., Luo, X., Huang, G., Chen, J. (2018) Murrangatin suppresses angiogenesis induced by tumor cell-derived media and inhibits AKT activation in zebrafish and endothelial cells. Drug design, development and therapy. 12:3107-3115.
Abstract
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping