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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.

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.

SUBMITTER: Heuberger DM

PROVIDER: S-EPMC9600560 | biostudies-literature | 2022 Oct

REPOSITORIES: biostudies-literature

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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.

Heuberger Dorothea M DM Wolint Petra P Jang Jae-Hwi JH Itani Saria S Jungraithmayr Wolfgang W Waschkies Conny F CF Meier-Bürgisser Gabriella G Andreoli Stefano S Spanaus Katharina K Schuepbach Reto A RA Calcagni Maurizio M Fahrni Christoph J CJ Buschmann Johanna J

Cancers 20221019 20

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 a ...[more]

PMID: 36291910

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Project description:In this work we demonstrate a novel method of methylation detection that utilises immunoaffinity to detect the presence of methylated DNA hybridised to a cDNA microarray. We use a monoclonal antibody specific to 5 methylcytosine to detect the presence of 5 methylcytosine in genomic DNA from human fibroblasts bearing the karyotype 45 XO. We report that over 2900 genes show the presence of methylation in this condition. We also report that 165 genes are consistently methylated in all replicates of these experiments. The methylated genes show a uniform distribution over all the chromosomes. The gene ontology of these also indicates no functional correlation between the genes that are methylated. We detect the presence of methylation in IGF2, an imprinted gene and thus known to harbour DNA methylation. The method is extremely specific and offers a quick and efficient way to analyse the methylation landscape on a high throughput scale. This method uses existing technology to assess methylation and thus can integrate very efficiently into any platform used. A method that detects DNA methylation that is not restricted to specific sequences would provide a useful platform to analyse methylation distribution among the genes in any given phenotypic condition.Availability of additional approaches to examine DNA methylation would lead to increase in our understanding of the methylome and would help define the intrinsic and extrinsic factors which govern it. Microarray based high throughput methods have been extensively used for gene expression analysis. The method described uses a microarray to analyse DNA methylation levels in a gene/cDNA/oligo specific manner. Here, genomic DNA is fragmented and used for hybridization to microarray slides. The presence of DNA cytosine methylation in the hybridized DNA is detected by employing Cy3 labelled anti 5mC( 5-methyl cytidine) antibody (monoclonal). The resolution provided by this method is dependent upon the microarray platform used. This method can be adapted to any platform thus enabling seamless integration with existing technology of gene expression analysis

Dataset Information

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

Publications

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

Similar Datasets

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