title: Effect of novel dinuclear platinum(II) complexes on redox status of MOLT-4 leukemic cells.
abstract: As the alkylating agents metabolism is accompanied by reactive oxygen species (ROS) generation, the aim of this study has been to compare the effect of cisplatin and novel platinum(II) complexes, Pt2(isopropylamine)4(berenil)2, Pt2(piperazine)4(berenil)2, Pt2(2-picoline)4(berenil)2, Pt2(3-picoline)4(berenil)2, Pt2(4-picoline)4(berenil)2, on the redox state of human leukemic T-cells line Molt-4. Treatment of Molt-4 with the novel complexes has shown that all compounds enhance total ROS and superoxide anion generation as well as change the activity of antioxidant enzymes such as superoxide dismutase, catalase, glutathione peroxidase and glutathione reductase. Moreover, all the above-mentioned compounds cause a decrease in the level of non-enzymatic antioxidants such as GSH as well as vitamin C, E and A. Such a situation is conducive to oxidative stress formation and oxidative modifications of cellular macromolecules. DNA damage of MOLT-4 leukemic cells is connected with 8-hydroxy-2'-deoxyguanosine and N7-methyldeoxyguanosine generation. The increased level of protein carbonyl groups and dityrosine indicates enhanced protein oxidative modifications, while an increase in the level of lipid peroxidation products, MDA, 4-HNE and isoprostanes proves the significant lipid peroxidation after treatment of Molt-4 cells with the complexes. Moreover, the complexes enhance expression of Bax and cytochrome c as well as decrease the expression of Bcl-2 and p53 protein. The novel platinum(II) complexes in comparison with cisplatin disturb redox status more intensively and lead to oxidative stress in Molt-4 cells. The enhanced oxidative modifications of macromolecules of human leukemic cancer cells lead to a shift in the proapoptotic-antiapoptotic balance into the proapoptotic direction.
authors.affiliation: Department of Analytical Chemistry and.
authors.forename: Iwona
authors.initials: I
authors.lastname: Jarocka
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Gęgotek
authors.forename: Anna
authors.initials: A
authors.lastname: Bielawska
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Bielawski
authors.forename: Wojciech
authors.initials: W
authors.lastname: Łuczaj
authors.forename: Tomasz
authors.initials: T
authors.lastname: Hodun
authors.forename: Elżbieta
authors.initials: E
authors.lastname: Skrzydlewska
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D000975:Antioxidants / Q000378:metabolism; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D015394:Molecular Structure; D009944:Organoplatinum Compounds / Q000737:chemistry / Q000494:pharmacology*; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000187:drug effects*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D013329:Structure-Activity Relationship; D013601:T-Lymphocytes / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D000975:Antioxidants; D009944:Organoplatinum Compounds; D017382:Reactive Oxygen Species; D002945:Cisplatin