High-affinity Cu(I) chelator PSP-2 as potential anti-angiogenic agent
Abstract
Copper is an essential trace metal that has been implicated in angiogenesis, the formation of new blood vessels. As tumor growth relies on establishing a functional capillary network for blood supply, copper chelation therapy may hold promise as an anti-cancer strategy by suppressing angiogenesis. To test the anti-angiogenic effect of PSP-2, a recently developed high affinity Cu(I) chelator with low zeptomolar dissociation constant, we utilized the endothelial cancer cell line EAhy926 and assessed changes in cell migration, proliferation, and tube formation in Matrigel. In addition, sprouting was assessed by the chicken and sheep aortic ring assay, and vascular pattern formation was studied in the chorioallantoic membrane of chicken embryos (CAM assay). While incubation with PSP-2 resulted in selective depletion of cellular copper levels, cell migration was not affected and the proliferating activity was even slightly increased. Moreover, the endothelial tube formation assay revealed significant morphological changes in the presence of PSP-2, with thicker tubular walls and an overall decreased meshes area. Similarly, the aortic ring assay and CAM assay showed that PSP-2 evokes significantly longer sprouts with smaller angles at branching points. Altogether, PSP-2 exhibits significant bioactivity at concentrations as low as 5 μM, rendering it a promising anti-angiogenic agent.more »
- Authors:
-
[2];
[1]
- Univ. Hospital Zurich (Switzerland)
- Georgia Inst. of Technology, Atlanta, GA (United States)
- Argonne National Lab. (ANL), Argonne, IL (United States)
- Publication Date:
- Research Org.:
- Argonne National Lab. (ANL), Argonne, IL (United States)
- Sponsoring Org.:
- National Institute of Health; USDOE Office of Science (SC), Basic Energy Sciences (BES)
- OSTI Identifier:
- 1630314
- Grant/Contract Number:
- AC02-06CH11357
- Resource Type:
- Accepted Manuscript
- Journal Name:
- Scientific Reports
- Additional Journal Information:
- Journal Volume: 9; Journal Issue: 1; Journal ID: ISSN 2045-2322
- Publisher:
- Nature Publishing Group
- Country of Publication:
- United States
- Language:
- English
- Subject:
- 60 APPLIED LIFE SCIENCES
Citation Formats
Heuberger, Dorothea M., Harankhedkar, Shefali, Morgan, Thomas, Wolint, Petra, Calcagni, Maurizio, Lai, Barry, Fahrni, Christoph J., and Buschmann, Johanna. High-affinity Cu(I) chelator PSP-2 as potential anti-angiogenic agent. United States: N. p., 2019.
Web. doi:10.1038/s41598-019-50494-5.
Heuberger, Dorothea M., Harankhedkar, Shefali, Morgan, Thomas, Wolint, Petra, Calcagni, Maurizio, Lai, Barry, Fahrni, Christoph J., & Buschmann, Johanna. High-affinity Cu(I) chelator PSP-2 as potential anti-angiogenic agent. United States. https://doi.org/10.1038/s41598-019-50494-5
Heuberger, Dorothea M., Harankhedkar, Shefali, Morgan, Thomas, Wolint, Petra, Calcagni, Maurizio, Lai, Barry, Fahrni, Christoph J., and Buschmann, Johanna. Tue .
"High-affinity Cu(I) chelator PSP-2 as potential anti-angiogenic agent". United States. https://doi.org/10.1038/s41598-019-50494-5. https://www.osti.gov/servlets/purl/1630314.
@article{osti_1630314,
title = {High-affinity Cu(I) chelator PSP-2 as potential anti-angiogenic agent},
author = {Heuberger, Dorothea M. and Harankhedkar, Shefali and Morgan, Thomas and Wolint, Petra and Calcagni, Maurizio and Lai, Barry and Fahrni, Christoph J. and Buschmann, Johanna},
abstractNote = {Copper is an essential trace metal that has been implicated in angiogenesis, the formation of new blood vessels. As tumor growth relies on establishing a functional capillary network for blood supply, copper chelation therapy may hold promise as an anti-cancer strategy by suppressing angiogenesis. To test the anti-angiogenic effect of PSP-2, a recently developed high affinity Cu(I) chelator with low zeptomolar dissociation constant, we utilized the endothelial cancer cell line EAhy926 and assessed changes in cell migration, proliferation, and tube formation in Matrigel. In addition, sprouting was assessed by the chicken and sheep aortic ring assay, and vascular pattern formation was studied in the chorioallantoic membrane of chicken embryos (CAM assay). While incubation with PSP-2 resulted in selective depletion of cellular copper levels, cell migration was not affected and the proliferating activity was even slightly increased. Moreover, the endothelial tube formation assay revealed significant morphological changes in the presence of PSP-2, with thicker tubular walls and an overall decreased meshes area. Similarly, the aortic ring assay and CAM assay showed that PSP-2 evokes significantly longer sprouts with smaller angles at branching points. Altogether, PSP-2 exhibits significant bioactivity at concentrations as low as 5 μM, rendering it a promising anti-angiogenic agent. As EAhy926 cells exhibit both endothelial and tumorigenic properties, the anti-angiogenic effect of PSP-2 might potentially translate also into anticancer activity.},
doi = {10.1038/s41598-019-50494-5},
journal = {Scientific Reports},
number = 1,
volume = 9,
place = {United States},
year = {2019},
month = {10}
}
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Figures / Tables:
Figure 1: SXRF elemental analysis. SXRF analysis of 3T3 mouse fibroblasts grown in medium supplemented with CuCl2 (50 µM) before (A,C,E) and after (B,D,F) treatment with the Cu(I)-selective high-affinity chelator PSP-2 (50 µM). (A,B) False-color elemental density maps for Cu and Zn. The minimum to maximum density range is indicatedmore »
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Works referenced in this record:
Angiogenesis Assays: A Critical Overview
journal, January 2003
- Auerbach, Robert; Lewis, Rachel; Shinners, Brenda
- Clinical Chemistry, Vol. 49, Issue 1
Binary Doping of Strontium and Copper Enhancing Osteogenesis and Angiogenesis of Bioactive Glass Nanofibers while Suppressing Osteoclast Activity
journal, July 2017
- Weng, Lin; Boda, Sunil Kumar; Teusink, Matthew J.
- ACS Applied Materials & Interfaces, Vol. 9, Issue 29
Copper chelator ATN-224 inhibits endothelial function by multiple mechanisms
journal, May 2009
- Lowndes, Sarah A.; Sheldon, Helen V.; Cai, Shijie
- Microvascular Research, Vol. 77, Issue 3
Anti-angiogenic effect of arsenic trioxide in lung cancer via inhibition of endothelial cell migration, proliferation and tube formation
journal, July 2017
- Yang, Meng-Hang; Chang, Ke-Jie; Zheng, Jin-Cheng
- Oncology Letters, Vol. 14, Issue 3
In Vitro Models of Angiogenesis: The use of Matrigel
journal, October 1999
- Benelli, R.; Albini, A.
- The International Journal of Biological Markers, Vol. 14, Issue 4
Angiogenic factors and their assay: Activity of formyl methionyl leucyl phenylalanine, adenosine diphosphate, heparin, copper, and bovine endothelium stimulating factor
journal, November 1983
- McAuslan, B. R.; Reilly, W. G.; Hannan, G. N.
- Microvascular Research, Vol. 26, Issue 3
Synthesis, Structural Characterization, and Antiangiogenic Activity of Polyfluorinated Benzamides
journal, September 2018
- Steinebach, Christian; Ambrożak, Agnieszka; Dosa, Stefan
- ChemMedChem, Vol. 13, Issue 19
Ratiometric two-photon microscopy reveals attomolar copper buffering in normal and Menkes mutant cells
journal, June 2019
- Morgan, M. Thomas; Bourassa, Daisy; Harankhedkar, Shefali
- Proceedings of the National Academy of Sciences, Vol. 116, Issue 25
Comparative Endothelial Cell Response on Topographically Patterned Titanium and Silicon Substrates with Micrometer to Sub-Micrometer Feature Sizes
journal, October 2014
- Vandrangi, Prashanthi; Gott, Shannon C.; Kozaka, Ryan
- PLoS ONE, Vol. 9, Issue 10
MiR-29b aggravates lipopolysaccharide-induced endothelial cells inflammatory damage by regulation of NF-κB and JNK signaling pathways
journal, March 2018
- Yuan, Huifeng; Ma, Ji; Li, Tengfei
- Biomedicine & Pharmacotherapy, Vol. 99
The chick embryo chorioallantoic membrane as a bioassay for angiogenesis factors: Reactions induced by carrier materials
journal, January 1978
- Jakob, W.; Jentzsch, K. D.; Mauersberger, B.
- Experimentelle Pathologie, Vol. 15, Issue 5
Iron and copper metabolism
journal, August 2005
- Arredondo, Miguel; Núñez, Marco T.
- Molecular Aspects of Medicine, Vol. 26, Issue 4-5
Graphene Oxide-Copper Nanocomposite-Coated Porous CaP Scaffold for Vascularized Bone Regeneration via Activation of Hif-1α
journal, March 2016
- Zhang, Wenjie; Chang, Qing; Xu, Ling
- Advanced Healthcare Materials, Vol. 5, Issue 11
Bioavailable copper modulates oxidative phosphorylation and growth of tumors
journal, November 2013
- Ishida, S.; Andreux, P.; Poitry-Yamate, C.
- Proceedings of the National Academy of Sciences, Vol. 110, Issue 48
Acrolein-induced autophagy–dependent apoptosis via activation of the lysosomal–mitochondrial pathway in EAhy926 cells
journal, October 2018
- Luo, Songsong; Jiang, Liping; Li, Qiannan
- Toxicology in Vitro, Vol. 52
The chick embryo chorioallantoic membrane as a model for tumor biology
journal, November 2014
- Ribatti, Domenico
- Experimental Cell Research, Vol. 328, Issue 2
Homoleptic phosphino copper( i ) complexes with in vitro and in vivo dual cytotoxic and anti-angiogenic activity
journal, January 2015
- Gandin, V.; Trenti, A.; Porchia, M.
- Metallomics, Vol. 7, Issue 11
Behind the Link between Copper and Angiogenesis: Established Mechanisms and an Overview on the Role of Vascular Copper Transport Systems
journal, October 2015
- Urso, Emanuela; Maffia, Michele
- Journal of Vascular Research, Vol. 52, Issue 3
Targeting copper in cancer therapy: ‘Copper That Cancer’
journal, January 2015
- Denoyer, Delphine; Masaldan, Shashank; La Fontaine, Sharon
- Metallomics, Vol. 7, Issue 11
Anti-angiogenic activity of para-coumaric acid methyl ester on HUVECs in vitro and zebrafish in vivo
journal, September 2018
- Zhang, He-Zhong; Li, Chong-Yong; Wu, Jia-Qi
- Phytomedicine, Vol. 48
MAPS : A set of software tools for analysis and visualization of 3D X-ray fluorescence data sets
journal, March 2003
- Vogt, S.
- Journal de Physique IV (Proceedings), Vol. 104
In vitro assays of angiogenesis for assessment of angiogenic and anti-angiogenic agents
journal, September 2007
- Goodwin, Anne M.
- Microvascular Research, Vol. 74, Issue 2-3
Evaluation of Curcumin Capped Copper Nanoparticles as Possible Inhibitors of Human Breast Cancer Cells and Angiogenesis: a Comparative Study with Native Curcumin
journal, October 2015
- Kamble, Sonali; Utage, Bhimashankar; Mogle, Pratima
- AAPS PharmSciTech, Vol. 17, Issue 5
Characterization and in ovo vascularization of a 3D-printed hydroxyapatite scaffold with different extracellular matrix coatings under perfusion culture
journal, October 2018
- Burgio, Floriana; Rimmer, Natalie; Pieles, Uwe
- Biology Open, Vol. 7, Issue 12
Stabilization of Aliphatic Phosphines by Auxiliary Phosphine Sulfides Offers Zeptomolar Affinity and Unprecedented Selectivity for Probing Biological Cu I
journal, July 2018
- Morgan, M. Thomas; Yang, Bo; Harankhedkar, Shefali
- Angewandte Chemie International Edition, Vol. 57, Issue 31
Subcellular redistribution and mitotic inheritance of transition metals in proliferating mouse fibroblast cells
journal, January 2013
- McRae, Reagan; Lai, Barry; Fahrni, Christoph J.
- Metallomics, Vol. 5, Issue 1
Synergy effects of copper and silicon ions on stimulation of vascularization by copper-doped calcium silicate
journal, January 2014
- Kong, Ni; Lin, Kaili; Li, Haiyan
- Journal of Materials Chemistry B, Vol. 2, Issue 8
Tetrathiomolybdate Inhibits Copper Trafficking Proteins Through Metal Cluster Formation
journal, November 2009
- Alvarez, H. M.; Xue, Y.; Robinson, C. D.
- Science, Vol. 327, Issue 5963
Anticopper therapy against cancer and diseases of inflammation and fibrosis
journal, August 2005
- Brewer, George J.
- Drug Discovery Today, Vol. 10, Issue 16
Copper-induced vascular endothelial growth factor expression and wound healing
journal, May 2002
- Sen, Chandan K.; Khanna, Savita; Venojarvi, Mika
- American Journal of Physiology-Heart and Circulatory Physiology, Vol. 282, Issue 5
X-ray fluorescence microscopy reveals large-scale relocalization and extracellular translocation of cellular copper during angiogenesis
journal, February 2007
- Finney, L.; Mandava, S.; Ursos, L.
- Proceedings of the National Academy of Sciences, Vol. 104, Issue 7
In vitro scratch assay: a convenient and inexpensive method for analysis of cell migration in vitro
journal, February 2007
- Liang, Chun-Chi; Park, Ann Y.; Guan, Jun-Lin
- Nature Protocols, Vol. 2, Issue 2
In vitro and in vivo evaluation of the anti-angiogenic actions of 4-hydroxybenzyl alcohol: Anti-angiogenic actions of HBA
journal, May 2011
- Laschke, Mw; van Oijen, AE Vorsterman; Scheuer, C.
- British Journal of Pharmacology, Vol. 163, Issue 4
Three-Dimensional Co-Cultures of Osteoblasts and Endothelial Cells in DegraPol Foam: Histological and High-Field Magnetic Resonance Imaging Analyses of Pre-Engineered Capillary Networks in Bone Grafts
journal, February 2011
- Buschmann, Johanna; Welti, Manfred; Hemmi, Sonja
- Tissue Engineering Part A, Vol. 17, Issue 3-4
A Requirement for Copper in Angiogenesis
journal, February 2004
- Harris, Edward D.
- Nutrition Reviews, Vol. 62, Issue 2
Enhanced Modulation of Keratinocyte Motility by Transforming Growth Factor-α (TGF-α) Relative to Epidermal Growth Factor (EGF)
journal, April 1996
- Cha, Donald; O'Brien, Patricia; O'Toole, Edel A.
- Journal of Investigative Dermatology, Vol. 106, Issue 4
A Requirement for Copper in Angiogenesis
journal, February 2004
- Harris, Edward D.
- Nutrition Reviews, Vol. 62, Issue 2
Graphene Oxide-Copper Nanocomposite-Coated Porous CaP Scaffold for Vascularized Bone Regeneration via Activation of Hif-1α
journal, March 2019
- Zhang, Wenjie; Chang, Qing; Xu, Ling
- Advanced Healthcare Materials, Vol. 8, Issue 5
Characterization and vascularization of a 3D-printed hydroxyapatite scaffold with different extracellular matrix coatings under perfusion culture
text, January 2018
- Burgio, Floriana; Rimmer, Natalie; Pieles, Uwe
- The Company of Biologists Ltd.
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