Light-induced anticancer activity of [RuCl2(DMSO)4] complexes.
The cytotoxicity and photocytotoxicity of trans-[RuCl2(DMSO)4] and cis-[RuCl2(DMSO)4] complexes was tested in two melanoma cell lines, human (SK-MEL 188) and mouse (S91). The trans isomer was found to be more effective for cell growth inhibition than its cis analogue both in the presence and in the absence of illumination. However, the antiproliferative activity of both isomers was significantly enhanced after irradiation with UVA light in comparison with their activity observed in the dark. The influence of light on the reaction of both ruthenium(II) isomers with the single-stranded hexanucleotide d(T2GGT2), chosen as a model system for DNA, was also studied using chromatography and mass spectrometry techniques. The photochemical reaction of the ruthenium(II) complexes with the oligonucleotide d(T2GGT2) resulted in the formation of Ru(G-N7)2 adducts, which was not observed in the same time scale in thermal reactions. The initial short irradiation of the inert cis isomer was found to facilitate the covalent adduct formation with d(T2GGT2) in the secondary thermal reactions and with a rate comparable to that found for the trans isomer, which is ca. 5-10 times more reactive in the dark.
Brindell
Małgorzata
M
Department of Inorganic Chemistry, Faculty of Chemistry, Jagiellonian University, Ingardena 3, 30-060 Krakow, Poland.
Kuliś
Ewa
E
Elmroth
Sofi K C
SK
Urbańska
Krystyna
K
Stochel
Grazyna
G
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology / Q000528:radiation effects; D045744:Cell Line, Tumor; D002851:Chromatography, High Pressure Liquid; D004247:DNA / Q000737:chemistry; D004121:Dimethyl Sulfoxide / Q000737:chemistry*; D004354:Drug Screening Assays, Antitumor; D006361:Heating; D006801:Humans; D006868:Hydrolysis; D008545:Melanoma; D051379:Mice; D009841:Oligonucleotides / Q000737:chemistry; D009942:Organometallic Compounds / Q000138:chemical synthesis* / Q000494:pharmacology / Q000528:radiation effects; D010782:Photolysis; D011355:Prodrugs / Q000138:chemical synthesis* / Q000494:pharmacology / Q000528:radiation effects; D012428:Ruthenium; D012996:Solutions; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D014466:Ultraviolet Rays; D014867:Water
D000970:Antineoplastic Agents; D009841:Oligonucleotides; D009942:Organometallic Compounds; D011355:Prodrugs; D012996:Solutions; D014867:Water; D012428:Ruthenium; D004247:DNA; D004121:Dimethyl Sulfoxide