Antitumor platinum(II) complex 56MESS binds to DNA G-quadruplexes, downregulates expression of c-MYC and k-RAS oncogenes, and triggers DNA damage in cancer cells
Language English Country Ireland Media print-electronic
Document type Journal Article
PubMed
40288436
DOI
10.1016/j.cbi.2025.111534
PII: S0009-2797(25)00164-4
Knihovny.cz E-resources
- Keywords
- Antitumor platinum complex, DNA G-quadruplex, DNA i-Motif, c-MYC oncogene, k-RAS oncogene,
- MeSH
- DNA metabolism chemistry MeSH
- Down-Regulation * drug effects MeSH
- G-Quadruplexes * drug effects MeSH
- Humans MeSH
- Cell Line, Tumor MeSH
- Organoplatinum Compounds * pharmacology chemistry MeSH
- DNA Damage * drug effects MeSH
- Cell Proliferation drug effects MeSH
- Antineoplastic Agents * pharmacology chemistry MeSH
- Proto-Oncogene Proteins c-myc * genetics metabolism MeSH
- Proto-Oncogene Proteins p21(ras) * genetics metabolism MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Names of Substances
- DNA MeSH
- Organoplatinum Compounds * MeSH
- Antineoplastic Agents * MeSH
- Proto-Oncogene Proteins c-myc * MeSH
- Proto-Oncogene Proteins p21(ras) * MeSH
Previous research indicated that the cytotoxic activity of the antitumor platinum(II) complex [Pt(1S,2S-diaminocyclohexane)(5,6-dimethyl-1,10-phenanthroline)]2+ (56MESS) was not primarily attributed to DNA binding, despite the complex being confirmed to localize also in the nucleus. In this study, we have demonstrated that the antiproliferative activity of 56MESS indeed involves DNA binding. Furthermore, in addition to binding duplex DNA, the complex also interacts with non-canonical secondary DNA structures, such as G-quadruplexes (G4s) and i-Motifs (iMs). This interaction leads to the suppression of G-regulated oncogene expression and disrupts key enzymatic processes associated with DNA, potentially contributing to DNA damage and the biological activity of 56MESS. These findings build upon previously published results, revealing that the anticancer activity of 56MESS is significantly more multifaceted than previously understood, involving multiple distinct mechanisms.
Department of Biophysics Faculty of Science Palacky University 783 71 Olomouc Czech Republic
Institute of Biophysics Czech Academy of Sciences CZ 61200 Brno Czech Republic
School of Science Western Sydney University Penrith South DC 1797 New South Wales Australia
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