Dextran-Catechin inhibits angiogenesis by disrupting copper homeostasis in endothelial cells

Abstract Formation of blood vessels, or angiogenesis, is crucial to cancer progression. Thus, inhibiting angiogenesis can limit the growth and spread of tumors. The natural polyphenol catechin has moderate anti-tumor activity and interacts with copper, which is essential for angiogenesis. Catechin i...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Eugene M. H. Yee, Miriam B. Brandl, Eddy Pasquier, Giuseppe Cirillo, Kathleen Kimpton, Maria Kavallaris, Naresh Kumar, Orazio Vittorio
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/86957e54d73e492ebf3c69aaf156aadd
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:86957e54d73e492ebf3c69aaf156aadd
record_format	dspace
spelling	oai:doaj.org-article:86957e54d73e492ebf3c69aaf156aadd2021-12-02T15:06:16ZDextran-Catechin inhibits angiogenesis by disrupting copper homeostasis in endothelial cells10.1038/s41598-017-07452-w2045-2322https://doaj.org/article/86957e54d73e492ebf3c69aaf156aadd2017-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-07452-whttps://doaj.org/toc/2045-2322Abstract Formation of blood vessels, or angiogenesis, is crucial to cancer progression. Thus, inhibiting angiogenesis can limit the growth and spread of tumors. The natural polyphenol catechin has moderate anti-tumor activity and interacts with copper, which is essential for angiogenesis. Catechin is easily metabolized in the body and this limits its clinical application. We have recently shown that conjugation of catechin with dextran (Dextran-Catechin) improves its serum stability, and exhibits potent anti-tumor activity against neuroblastoma by targeting copper homeostasis. Herein, we investigated the antiangiogenic activity of Dextran-Catechin and its mechanism. We found that Dextran-Catechin displayed potent antiangiogenic activity in vitro and in vivo. We demonstrated Dextran-Catechin generates reactive oxygen species which in turns disrupts copper homeostasis by depleting the copper importer CTR-1 and copper trafficking ATOX-1 protein. Mechanistically, we showed that disrupting copper homeostasis by knockdown of either CTR-1 or ATOX-1 protein can inhibit angiogenesis in endothelial cells. This data strongly suggests the Dextran-Catechin potent antiangiogenic activity is mediated by disrupting copper homeostasis. Thus, compounds such as Dextran-Catechin that affects both tumor growth and angiogenesis could lead the way for development of new drugs against high copper levels tumors.Eugene M. H. YeeMiriam B. BrandlEddy PasquierGiuseppe CirilloKathleen KimptonMaria KavallarisNaresh KumarOrazio VittorioNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-10 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Eugene M. H. Yee Miriam B. Brandl Eddy Pasquier Giuseppe Cirillo Kathleen Kimpton Maria Kavallaris Naresh Kumar Orazio Vittorio Dextran-Catechin inhibits angiogenesis by disrupting copper homeostasis in endothelial cells
description	Abstract Formation of blood vessels, or angiogenesis, is crucial to cancer progression. Thus, inhibiting angiogenesis can limit the growth and spread of tumors. The natural polyphenol catechin has moderate anti-tumor activity and interacts with copper, which is essential for angiogenesis. Catechin is easily metabolized in the body and this limits its clinical application. We have recently shown that conjugation of catechin with dextran (Dextran-Catechin) improves its serum stability, and exhibits potent anti-tumor activity against neuroblastoma by targeting copper homeostasis. Herein, we investigated the antiangiogenic activity of Dextran-Catechin and its mechanism. We found that Dextran-Catechin displayed potent antiangiogenic activity in vitro and in vivo. We demonstrated Dextran-Catechin generates reactive oxygen species which in turns disrupts copper homeostasis by depleting the copper importer CTR-1 and copper trafficking ATOX-1 protein. Mechanistically, we showed that disrupting copper homeostasis by knockdown of either CTR-1 or ATOX-1 protein can inhibit angiogenesis in endothelial cells. This data strongly suggests the Dextran-Catechin potent antiangiogenic activity is mediated by disrupting copper homeostasis. Thus, compounds such as Dextran-Catechin that affects both tumor growth and angiogenesis could lead the way for development of new drugs against high copper levels tumors.
format	article
author	Eugene M. H. Yee Miriam B. Brandl Eddy Pasquier Giuseppe Cirillo Kathleen Kimpton Maria Kavallaris Naresh Kumar Orazio Vittorio
author_facet	Eugene M. H. Yee Miriam B. Brandl Eddy Pasquier Giuseppe Cirillo Kathleen Kimpton Maria Kavallaris Naresh Kumar Orazio Vittorio
author_sort	Eugene M. H. Yee
title	Dextran-Catechin inhibits angiogenesis by disrupting copper homeostasis in endothelial cells
title_short	Dextran-Catechin inhibits angiogenesis by disrupting copper homeostasis in endothelial cells
title_full	Dextran-Catechin inhibits angiogenesis by disrupting copper homeostasis in endothelial cells
title_fullStr	Dextran-Catechin inhibits angiogenesis by disrupting copper homeostasis in endothelial cells
title_full_unstemmed	Dextran-Catechin inhibits angiogenesis by disrupting copper homeostasis in endothelial cells
title_sort	dextran-catechin inhibits angiogenesis by disrupting copper homeostasis in endothelial cells
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/86957e54d73e492ebf3c69aaf156aadd
work_keys_str_mv	AT eugenemhyee dextrancatechininhibitsangiogenesisbydisruptingcopperhomeostasisinendothelialcells AT miriambbrandl dextrancatechininhibitsangiogenesisbydisruptingcopperhomeostasisinendothelialcells AT eddypasquier dextrancatechininhibitsangiogenesisbydisruptingcopperhomeostasisinendothelialcells AT giuseppecirillo dextrancatechininhibitsangiogenesisbydisruptingcopperhomeostasisinendothelialcells AT kathleenkimpton dextrancatechininhibitsangiogenesisbydisruptingcopperhomeostasisinendothelialcells AT mariakavallaris dextrancatechininhibitsangiogenesisbydisruptingcopperhomeostasisinendothelialcells AT nareshkumar dextrancatechininhibitsangiogenesisbydisruptingcopperhomeostasisinendothelialcells AT oraziovittorio dextrancatechininhibitsangiogenesisbydisruptingcopperhomeostasisinendothelialcells
_version_	1718388525911506944

Dextran-Catechin inhibits angiogenesis by disrupting copper homeostasis in endothelial cells

Ejemplares similares