Marine Bromophenol Bis(2,3,6-Tribromo-4,5-Dihydroxybenzyl)ether Inhibits Angiogenesis in Human Umbilical Vein Endothelial Cells and Reduces Vasculogenic Mimicry in Human Lung Cancer A549 Cells.

Songtao Dong,Ming Liu,Dimitrios Stagos,Yankai Liu,Xiukun Lin,Zhongyuan Chen,Li Wang

doi:10.3390/md19110641

Abstract

Angiogenesis, including the growth of new capillary blood vessels from existing ones and the malignant tumors cells formed vasculogenic mimicry, is quite important for the tumor metastasis. Anti-angiogenesis is one of the significant therapies in tumor treatment, while the clinical angiogenesis inhibitors usually exhibit endothelial cells dysfunction and drug resistance. Bis(2,3,6-tribromo-4,5-dihydroxybenzyl)ether (BTDE), a marine algae-derived bromophenol compound, has shown various biological activities, however, its anti-angiogenesis function remains unknown. The present study illustrated that BTDE had anti-angiogenesis effect in vitro through inhibiting human umbilical vein endothelial cells migration, invasion, tube formation, and the activity of matrix metalloproteinases 9 (MMP9), and in vivo BTDE also blocked intersegmental vessel formation in zebrafish embryos. Moreover, BTDE inhibited the migration, invasion, and vasculogenic mimicry formation of lung cancer cell A549. All these results indicated that BTDE could be used as a potential candidate in anti-angiogenesis for the treatment of cancer.

Highlights

Angiogenesis, the growth of new capillary blood vessels from existing ones and capillary venules, involves vascular endothelial cell proliferation, migration, matrix degradation, and branching to form new tubes [1]
In order to investigate the anti-angiogenesis activity of BTDE both in vitro and in vivo, we evaluated the effects of BTDE on the migration, invasion, tube formation, and matrix metalloproteinases 9 (MMP9) activity on HUVECs model, and on the growth of intersegmental blood vessel (ISV) in vivo using zebrafish embryos model
In addition to study whether BTDE inhibited the endothelial angiogenesis, we investigated the impact of BTDE on non-small cell lung cancer (NSCLC) vasculogenic mimicry

Summary

Introduction

Angiogenesis, the growth of new capillary blood vessels from existing ones and capillary venules, involves vascular endothelial cell proliferation, migration, matrix degradation, and branching to form new tubes [1]. It has been recognized as a proven sign in tumor growth and metastasis on account of the functional blood supply [2]. Bevacizumab, the recombinant humanized monoclonal antibody, playing obvious anti-angiogenesis effect, has been used clinically to treat various malignant tumors through binding with VEGF [6]. Another anti-tumor drug ENDOSTAR, inhibits cancer angiogenesis through targeting vascular

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Conclusion