High-affinity Cu(I) Chelator PSP-2 As Potential Anti-angiogenic Agent
Authors
Affiliations
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 anti-cancer activity.
Cuproptosis: molecular mechanisms, cancer prognosis, and therapeutic applications.
Cong Y, Li N, Zhang Z, Shang Y, Zhao H J Transl Med. 2025; 23(1):104.
PMID: 39844182 PMC: 11752808. DOI: 10.1186/s12967-025-06121-1.
Standardization to Characterize the Complexity of Vessel Network Using the Aortic Ring Model.
Wolint P, Hofmann S, von Atzigen J, Boni R, Miescher I, Giovanoli P Int J Mol Sci. 2025; 26(1.
PMID: 39796147 PMC: 11719671. DOI: 10.3390/ijms26010291.
Selective binding and removal of copper from biological fluids-why are PSP ligands so efficient?.
Faller P J Biol Inorg Chem. 2024; 29(7-8):639-640.
PMID: 39613974 DOI: 10.1007/s00775-024-02082-w.
Nabatilan A, Thomas Morgan M, Netzer S, Fahrni C J Biol Inorg Chem. 2024; 29(5):531-540.
PMID: 39066798 DOI: 10.1007/s00775-024-02065-x.
Yu J, Bacsa J, Fahrni C Inorg Chem. 2023; 62(4):1287-1296.
PMID: 36661323 PMC: 10118051. DOI: 10.1021/acs.inorgchem.2c03524.