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High-Affinity Cu(I)-Chelator with Potential Anti-Tumorigenic Action—A Proof-of-Principle Experimental Study of Human H460 Tumors in the CAM Assay.
- Source :
- Cancers; Oct2022, Vol. 14 Issue 20, p5122-N.PAG, 14p
- Publication Year :
- 2022
-
Abstract
- Simple Summary: Lung cancer is a serious burden worldwide. The growth of lung tumors depends on vessel density and intratumoral copper concentration. Copper chelating agents can reduce copper content in tumor tissue, resulting in lower vessel density and lower tumor weight. PSP-2, a very potent copper chelator, was tested on lung tumor grafts that were on-planted on the chorioallantoic membrane of the chicken embryo. We found a lower vessel density and a lower tumor weight under PSP-2 application compared to the controls. Thus, PSP-2 could be a potential therapeutic agent to treat lung cancer in the future. 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<superscript>+</superscript> cell numbers at a low dose but increased cell count under a high dose. Moreover, HIF-1α<superscript>+</superscript> 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. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 20726694
- Volume :
- 14
- Issue :
- 20
- Database :
- Complementary Index
- Journal :
- Cancers
- Publication Type :
- Academic Journal
- Accession number :
- 159914679
- Full Text :
- https://doi.org/10.3390/cancers14205122