Anticancer potential of a photoactivated transplatin derivative containing the methylazaindole ligand mediated by ROS generation and DNA cleavage
Language English Country Great Britain, England Media print
Document type Journal Article
PubMed
27396365
DOI
10.1039/c6dt01467d
Knihovny.cz E-resources
- MeSH
- Cisplatin * chemistry pharmacology radiation effects MeSH
- DNA drug effects metabolism MeSH
- DNA Fragmentation MeSH
- Indoles * chemistry pharmacology radiation effects MeSH
- Humans MeSH
- Ligands MeSH
- Cell Line, Tumor MeSH
- Antineoplastic Agents * chemistry pharmacology radiation effects MeSH
- Reactive Oxygen Species metabolism MeSH
- Singlet Oxygen chemistry MeSH
- DNA Cleavage MeSH
- Ultraviolet Rays MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Names of Substances
- Cisplatin * MeSH
- DNA MeSH
- Indoles * MeSH
- Ligands MeSH
- Antineoplastic Agents * MeSH
- Reactive Oxygen Species MeSH
- Singlet Oxygen MeSH
- transplatin MeSH Browser
The limitations associated with the clinical utility of conventional platinum anticancer drugs have stimulated research leading to the design of new metallodrugs with improved pharmacological properties, particularly with increased selectivity for cancer cells. Very recent research has demonstrated that photoactivation or photopotentiation of platinum drugs can be one of the promising approaches to tackle this challenge. This is so because the application of irradiation can be targeted exclusively to the tumor tissue so that the resulting effects could be much more selective and targeted to the tumor. We show in this work that the presence of 1-methyl-7-azaindole in trans-[PtCl2(NH3)(L)] (L = 1-methyl-7-azaindole, compound 1) markedly potentiated the DNA binding ability of 1 when irradiated by UVA light in a cell-free medium. Concomitantly, the formation of cytotoxic bifunctional cross-links was markedly enhanced. In addition, 1, when irradiated with UVA, was able to effectively cleave the DNA backbone also in living cells. The incorporation of 1-methyl-7-azaindole moiety had also a profound effect on the photophysical properties of 1, which can generate singlet oxygen responsible for the DNA cleavage reaction. Finally, we found that 1, upon irradiation with UVA light, exhibited a pronounced dose-dependent decrease in viability of A2780 cells whereas it was markedly less cytotoxic if the cells were treated in the absence of light. Hence, it is possible to conclude that 1 is amenable to photodynamic therapy.
References provided by Crossref.org
In vitro anticancer active cis-Pt(II)-diiodido complexes containing 4-azaindoles
