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.