High-Affinity Cu(I)-Chelator with Potential Anti-Tumorigenic Action—A Proof-of-Principle Experimental Study of Human H460 Tumors in the CAM Assay

Abstract

Human lung cancer ranks among the most frequently treated cancers worldwide. As copper appears critical to angiogenesis and tumor growth, selective removal of copper represents a promising strategy to restrict tumor growth. To this end, we explored the activity of the novel high-affinity membrane-permeant Cu(I) chelator PSP-2 featuring a low-zeptomolar dissociation constant. Using H460 human lung cancer cells, we generated small tumors on the chorioallantoic membrane of the chicken embryo (CAM assay) and studied the effects of topical PSP-2 application on their weight and vessel density after one week. We observed a significant angiosuppression along with a marked decrease in tumor weight under PSP-2 application compared to controls. Moreover, PSP-2 exposure resulted in lower ki67+ cell numbers at a low dose but increased cell count under a high dose. Moreover, HIF-1α+ cells were significantly reduced with low-dose PSP-2 exposure compared to high-dose and control. The total copper content was considerably lower in PSP-2 treated tumors, although statistically not significant. Altogether, PSP-2 shows promising potential as an anti-cancer drug. Nevertheless, further animal experiments and application to different tumor types are mandatory to support these initial findings, paving the way toward clinical trials.

Ultrasonic Coating of Poly(D,L-lactic acid)/Poly(lactic-co-glycolic acid) Electrospun Fibers with ZnO Nanoparticles to Increase Angiogenesis in the CAM Assay

“…We furthermore demonstrated a significantly improved vascularization in presence of ZnO NPs. Using the CAM assay, a typical model system to study angiogenesis [ 48 , 50 , 51 , 56 , 59 ], we compared four groups with different concentrations of ZnO NPs, constructed from two different NP sizes (A = 25 nm, B = 70 nm) and two different sonocoating times (0.5 or 1 s), to the plain PDLLA/PLGA biopolymer scaffold. Previous studies have shown the angiogenic properties of ZnO NPs by analyzing the CAM and CAM-scaffold interface vessels [ 20 , 58 ].…”

Transition metals in angiogenesis – A narrative review

“…The lack of copper has led to inferior angiogenic responses in rabbit models [ 134 ]. These findings concerning copper's proangiogenic effects have led scientists to develop treatments to inhibit copper in cancers through chelation to inhibit vascularization and metastasis [ 129 , 135 ]. For example molybdenum in tetrathiomolybdate (TTM) has been proven to chelate copper, resulting in antiangiogenic effects [ 136 ].…”

Editorial for Special Issue: The Chorioallantoic Membrane (CAM) Model—Traditional and State-of-the Art Applications: The 1st International CAM Conference

“…Demcisakova et al analyzed the vascularization potential of biomaterial scaffolds that were positioned on the CAM as a test model for novel bone repair materials [3]. Heuberger et al reported that the potential anti-cancer effect of copper chelators was mostly mediated through angiosuppression [4]. Faihs et al introduced the application of a novel image analysis software for angiogenesis research [5].…”