Photo-induced DNA cleavage and cytotoxicity of a ruthenium(II) arene anticancer complex

0461985 - BFÚ 2017 RIV US eng J - Journal Article
Brabec, Viktor - Prachařová, J. - Štěpánková, Jana - Sadler, P. J. - Kašpárková, Jana
Photo-induced DNA cleavage and cytotoxicity of a ruthenium(II) arene anticancer complex.
Journal of Inorganic Biochemistry. Roč. 160, JUL2016 (2016), s. 149-155. ISSN 0162-0134. E-ISSN 1873-3344
R&D Projects: GA ČR(CZ) GA14-21053S; GA MŠMT(CZ) LD14019
Institutional support: RVO:68081707
Keywords : Ruthenium anticancer complex * DNA cleavage * Phototoxicity
Subject RIV: BO - Biophysics
Impact factor: 3.348, year: 2016

We report DNA cleavage by ruthenium(II) arene anticancer complex [(eta(6)-p-terp)Ru-II(en)Cl](+) (p-terp = paraterphenyl, 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 (O-1(2)) 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.
Permanent Link: http://hdl.handle.net/11104/0261526