Photo-induced DNA cleavage and cytotoxicity of a ruthenium(II) arene anticancer complex
Jazyk angličtina Země Spojené státy americké Médium print-electronic
Typ dokumentu časopisecké články, práce podpořená grantem
Grantová podpora
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-zdroje
- Klíčová slova
- Antitumor activity, Comet assay, DNA cleavage, Photodynamic chemotherapy, Phototoxicity, Ruthenium anticancer complex,
- MeSH
- DNA chemie MeSH
- ethylendiaminy chemie MeSH
- fotochemoterapie MeSH
- kationty dvojmocné MeSH
- komplexní sloučeniny chemická syntéza farmakologie MeSH
- lidé MeSH
- nádorové buněčné linie MeSH
- organokovové sloučeniny chemická syntéza farmakologie MeSH
- plazmidy chemie MeSH
- protinádorové látky chemická syntéza farmakologie MeSH
- ruthenium chemie MeSH
- sekvence nukleotidů MeSH
- singletový kyslík chemie MeSH
- štěpení DNA účinky léků účinky záření MeSH
- světlo MeSH
- terfenylové sloučeniny chemie MeSH
- viabilita buněk účinky léků účinky záření MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- DNA MeSH
- ethylendiaminy MeSH
- ethylenediamine MeSH Prohlížeč
- kationty dvojmocné MeSH
- komplexní sloučeniny MeSH
- organokovové sloučeniny MeSH
- protinádorové látky MeSH
- ruthenium MeSH
- singletový kyslík MeSH
- terfenylové sloučeniny 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.
Citace poskytuje Crossref.org
