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

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.