Photo-induced DNA cleavage and cytotoxicity of a ruthenium(II) arene anticancer complex
Language English Country United States Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
Grant support
247450
European Research Council - International
G0701062
Medical Research Council - United Kingdom
PubMed
26778426
DOI
10.1016/j.jinorgbio.2015.12.029
PII: S0162-0134(15)30155-0
Knihovny.cz E-resources
- Keywords
- Antitumor activity, Comet assay, DNA cleavage, Photodynamic chemotherapy, Phototoxicity, Ruthenium anticancer complex,
- MeSH
- DNA chemistry MeSH
- Ethylenediamines chemistry MeSH
- Photochemotherapy MeSH
- Cations, Divalent MeSH
- Coordination Complexes chemical synthesis pharmacology MeSH
- Humans MeSH
- Cell Line, Tumor MeSH
- Organometallic Compounds chemical synthesis pharmacology MeSH
- Plasmids chemistry MeSH
- Antineoplastic Agents chemical synthesis pharmacology MeSH
- Ruthenium chemistry MeSH
- Base Sequence MeSH
- Singlet Oxygen chemistry MeSH
- DNA Cleavage drug effects radiation effects MeSH
- Light MeSH
- Terphenyl Compounds chemistry MeSH
- Cell Survival drug effects radiation effects MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- DNA MeSH
- Ethylenediamines MeSH
- ethylenediamine MeSH Browser
- Cations, Divalent MeSH
- Coordination Complexes MeSH
- Organometallic Compounds MeSH
- Antineoplastic Agents MeSH
- Ruthenium MeSH
- Singlet Oxygen MeSH
- Terphenyl Compounds MeSH
We report DNA cleavage by ruthenium(II) arene anticancer complex [(η(6)-p-terp)Ru(II)(en)Cl](+) (p-terp=para-terphenyl, en=1,2-diaminoethane, complex 1) after its photoactivation by UVA and visible light, and the toxic effects of photoactivated 1 in cancer cells. It was shown in our previous work (T. Bugarcic et al., J. Med. Chem. 51 (2008) 5310-5319) that this complex exhibits promising toxic effects in several human tumor cell lines and concomitantly its DNA binding mode involves combined intercalative and monofunctional (coordination) binding modes. We demonstrate in the present work that when photoactivated by UVA or visible light, 1 efficiently photocleaves DNA, also in hypoxic media. Studies of the mechanism underlying DNA cleavage by photoactivated 1 reveal that the photocleavage reaction does not involve generation of reactive oxygen species (ROS), although contribution of singlet oxygen ((1)O2) to the DNA photocleavage process cannot be entirely excluded. Notably, the mechanism of DNA photocleavage by 1 appears to involve a direct modification of mainly those guanine residues to which 1 is coordinatively bound. As some tumors are oxygen-deficient and cytotoxic effects of photoactivated ruthenium compounds containing {Ru(η(6)-arene)}(2+) do not require the presence of oxygen, this class of ruthenium complexes may be considered potential candidate agents for improved photodynamic anticancer chemotherapy.
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