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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
J. Malina, H. Kostrhunova, JR. Aldrich-Wright, V. Brabec
Jazyk angličtina Země Irsko
Typ dokumentu časopisecké články
- MeSH
- DNA metabolismus chemie MeSH
- down regulace * účinky léků MeSH
- G-kvadruplexy * účinky léků MeSH
- lidé MeSH
- nádorové buněčné linie MeSH
- organoplatinové sloučeniny * farmakologie chemie MeSH
- poškození DNA * účinky léků MeSH
- proliferace buněk účinky léků MeSH
- protinádorové látky * farmakologie chemie MeSH
- protoonkogenní proteiny c-myc * genetika metabolismus MeSH
- protoonkogenní proteiny p21(ras) * genetika metabolismus MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články 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
Citace poskytuje Crossref.org
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- $a 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.
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