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Title: 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 » As EAhy926 cells exhibit both endothelial and tumorigenic properties, the anti-angiogenic effect of PSP-2 might potentially translate also into anticancer activity.« less

Authors:
 [1];  [2]; ORCiD logo [2];  [1];  [1];  [3];  [2]; ORCiD logo [1]
  1. Univ. Hospital Zurich (Switzerland)
  2. Georgia Inst. of Technology, Atlanta, GA (United States)
  3. 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. 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., & 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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