title: Photochemical properties of camptothecin in the presence of copper(II) ions: the role of radicals as prospective species in photodynamic therapy.
abstract: Camptothecin (CPT) is an anticancer drug that inhibits topoisomerase I (Topo I) by forming a ternary DNA-CPT-Topo I complex. However, it has also been shown that UVA-irradiated CPT in the absence of Topo I produces significant DNA damage to cancer cells. In this work, we explored and identified free radicals generated in these processes. From the low-temperature EPR spectrum of Cu(II)-CPT complex, a proximity between Cu(II) ion and 20-hydroxy group of lactone E ring of CPT is proposed. Upon irradiation (lambda = 365 nm) of the Cu(II)-CPT complex in de-oxygenated dimethylsulfoxide (DMSO), the EPR signal of Cu(II) measured in situ at room temperature shows formal first-order exponential decay with a formal half-life of 11 min. By the use of a specific Cu(I) chelating agent, neocuproine, it was shown that, during this process, Cu(II) is reduced to Cu(I). The loss in EPR signal intensity of the Cu(II)-CPT complex upon irradiation is accompanied by the appearance of a new EPR signal at g approximately 2.0022. Application of the spin trap nitrosodurene (ND) revealed that the main radical product formed upon continuous irradiation of CPT in DMSO solutions is the hydroxyl radical (trapped in DMSO as the *CH3 adduct) and superoxide radical. Application of 2,2,6,6-tetramethyl-4-piperidinol has revealed that irradiation of CPT in aerated DMSO solution also leads to formation of singlet oxygen (1O2). Our spectroscopic experiments indicate that CPT is a promising photosensitizer and that radicals and singlet oxygen generated upon illumination play a central role in DNA cleavage and in the induction of apoptosis in cancer cells.
authors.affiliation: Faculty of Chemical and Food Technology, Slovak University of Technology in Bratislava, Slovakia.
authors.forename: Vlasta
authors.initials: V
authors.lastname: Brezová
authors.forename: Dana
authors.initials: D
authors.lastname: Dvoranová
authors.forename: Vladimír
authors.initials: V
authors.lastname: Zúbor
authors.forename: Martin
authors.initials: M
authors.lastname: Breza
authors.forename: Milan
authors.initials: M
authors.lastname: Mazúr
authors.forename: Marián
authors.initials: M
authors.lastname: Valko
mesh_terms: D002166:Camptothecin / Q000737:chemistry* / Q000494:pharmacology / Q000528:radiation effects*; D003300:Copper / Q000737:chemistry*; D004247:DNA / Q000737:chemistry / Q000187:drug effects; D053837:DNA Cleavage; D004578:Electron Spin Resonance Spectroscopy; D005609:Free Radicals / Q000032:analysis; D006801:Humans; D010777:Photochemistry; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000737:chemistry* / Q000494:pharmacology / Q000528:radiation effects*; D014466:Ultraviolet Rays
chemical_list: D005609:Free Radicals; D017319:Photosensitizing Agents; D003300:Copper; D004247:DNA; D002166:Camptothecin