Oncotarget’s cover paper this week (Volume 12, Issue 15) is entitled, "Terpyridine platinum compounds induce telomere dysfunction and chromosome instability in cancer cells."
About the Study:
Researchers from the National Institutes of Health, University Paris-Saclay, Kazusa DNA Research Institute, and the University of Edinburgh used a dual-Human Artificial Chromosome (HAC) assay to analyze the genomic activity of six telomere-targeting platinum compounds.
The dual-HAC assay was previously created by the researchers in this study to detect compounds that induce CIN through telomere dysfunction. This assay consists of two cell lines: one with telomeres, and one without. Disruption of the cell lines with telomeres denotes compound-induced CIN, and indicates potentially efficacious cancer therapeutics in vivo.
“Recently we developed a dual-HAC-based assay allowing quantitative comparison of the efficiency and specificity of compounds to induce telomere dysfunction [36].”
Pt-tpy, a terpyridine platinum compound, and five of its structurally modified derivatives were assayed to determine their efficacy in creating genomic instability in cancer cells via telomere disruption. The team evaluated the six compounds using two isogenic human fibrosarcoma cell lines, the dual-HAC assay, FISH analysis of EGFP-HACs, telomere fluorescent in situ hybridization (Telo-FISH), flow cytometry, calculation of the rate of spontaneous HAC loss and after compound treatment, cell viability testing for measuring HAC loss in response to drug treatment, cytokinesis-block micronucleus assay, immunofluorescence, and statistical analysis.
“We found that treatment of cancer cells with either Pt-cpym, Pt-vpym, Pt-ttpy or Pt-tpy induces telomere dysfunction leading to high levels of chromosome instability.”
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DOI - https://doi.org/10.18632/oncotarget.28020
Full text - https://www.oncotarget.com/article/28020/text/
Correspondence to - Vladimir Larionov - larionov@mail.nih.gov and Natalay Kouprina - kouprinn@mail.nih.gov
Keywords - chromosome instability, CIN, platinum-derived G4-quadruplexes, telomere dysfunction, human artificial chromosome
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