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

Journal of Inorganic Biochemistry
Viktor BrabecJana Kasparkova

Abstract

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 {R...Continue Reading

Citations

Nov 3, 2016·Dalton Transactions : an International Journal of Inorganic Chemistry·Jian ZhaoCharles J Walsby
Jul 9, 2017·Chemistry : a European Journal·Zhen Yu, James A Cowan
May 10, 2018·Dalton Transactions : an International Journal of Inorganic Chemistry·Thomas N RohrabaughClaudia Turro
Jul 12, 2016·Dalton Transactions : an International Journal of Inorganic Chemistry·Jitka PracharovaViktor Brabec
Sep 27, 2019·Dalton Transactions : an International Journal of Inorganic Chemistry·Monize M da SilvaAlzir A Batista
Mar 17, 2020·Journal of Biomolecular Structure & Dynamics·Shazia ParveenLoic Toupet

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