title: Dinuclear berenil-platinum (II) complexes as modulators of apoptosis in human MCF-7 and MDA-MB231 breast cancer cells.
abstract: The metabolism of alkylating agents is accompanied by the generation of reactive oxygen species. The aim of this study was to treat estrogen receptor-positive and estrogen receptor-negative human breast cancer cells, MCF-7 and MDA-MB-231, respectively, with cisplatin and five different berenil-platinum (II) complexes, and then to investigate the oxidative modifications of DNA, lipid and protein, and to compare them with the profile of various pro- and antiapoptotic proteins. Changes in the levels of 8-hydroxy-2'-deoxyguanosine, 4-hydroxynonenal, carbonyl groups, dityrosine, active caspases 3, 8 and 9, as well as the expression of Bcl-2, Bax, cytochrome c, and p53 were subsequently examined. Activities of superoxide dismutase, catalase and glutathione, vitamin C levels were also investigated. Cellular reactions to cisplatin and the berenil-platinum (II) derivatives were more pronounced in MCF-7 cells as compared with the MDA-MB231 cells. Furthermore, the berenil-platinum (II) derivatives were found to be more effective than cisplatin. All of the complexes reduced the activity of superoxide dismutase and catalase, and also lowered the levels of non-enzymatic antioxidants. Increased level of lipid, protein as well as DNA damage markers was also observed after berenil-platinum (II) derivatives treatment. Similarly, the increase in the levels of the proapoptotic factors, were detected in MCF-7 and MDA-MB231 cells. Incubation of examined cells with the berenil-platinum (II) complexes also led to the increase in the levels of active caspases 3, 8 and 9. In conclusion, the results of the present study demonstrated that berenil-platinum (II) complexes more efficiently mediate cellular oxidative modifications and proapoptotic metabolism, particularly in MCF-7 cells, compared to cisplatin. Pt2(isopropylamine)4berenil2 and Pt2(piperidine)4(berenil)2 notably affected the cellular metabolism of estrogen-positive breast cancer cells. Thus, these complexes may be valuable for the design of additional anticancer drugs.
authors: Gęgotek
authors: G
authors: Agnieszka
authors: Ambrożewicz
authors: A
authors: Ewa
authors: Bielawska
authors: B
authors: Anna
authors: Bielawski
authors: B
authors: Krzysztof
authors: Cyuńczyk
authors: C
authors: Monika
authors: Department of Inorganic and Analytical Chemistry, Medical University of Bialystok; Mickiewicza 2D, 15-222 Bialystok, Poland. skrzydle@umb.edu.pl.
authors: Skrzydlewska
authors: S
authors: Elżbieta
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology*; D045744:Cell Line, Tumor; D004249:DNA Damage; D004133:Diminazene / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D005260:Female; D006801:Humans; D008055:Lipids / Q000737:chemistry; D009944:Organoplatinum Compounds / Q000737:chemistry / Q000494:pharmacology*; D010084:Oxidation-Reduction; D011960:Receptors, Estrogen / Q000378:metabolism*
chemical_list: D000970:Antineoplastic Agents; D051017:Apoptosis Regulatory Proteins; D008055:Lipids; D009944:Organoplatinum Compounds; D011960:Receptors, Estrogen; C110112:platinum-berenil; D004133:Diminazene