title: Cytotoxicity and induction of apoptosis of human breast cancer cells by novel platinum(II) complexes.
abstract: The current work investigates the influence of novel dinuclear platinum(II) compounds of structure: Pt2(3-ethylpyridine)4(berenil)2 (Pt10) and Pt2(3-butylpyridine)4(berenil)2 (Pt11) on growth and viability of MDA-MB-231 and MCF-7 breast cancer cells as well as their putative mechanism of cytotoxicity. Evaluation of the cytotoxicity of Pt10 and Pt11 employing a MTT assay and inhibition of [(3)H]thymidine incorporation into DNA in both MDA-MB-231 and MCF-7 breast cancer cells demonstrated that these compounds were more potent antiproliferative agents than cisplatin. In our study the induction of apoptosis by Pt10 and Pt11 in human breast cancer cells was confirmed by several biochemical markers, such as: phosphatidylserine externalization, loss of mitochondrial membrane potential ΔΨm, caspase-3, -8, -9 activity, and DNA degradation. Pt10 and Pt11 induce apoptosis of breast cancer cells via mechanisms dependent on caspases activation and associated with mitochondrial membrane potential disruption.
authors: Department of Medicinal Chemistry, Medical University of Białystok, Kilińskiego 1, 15-089 Białystok, Poland. kbiel@umwb.edu.pl
authors: Krzysztof
authors: K
authors: Bielawski
authors: Robert
authors: R
authors: Czarnomysy
authors: Anna
authors: A
authors: Muszyńska
authors: Anna
authors: A
authors: Bielawska
authors: Bożena
authors: B
authors: Popławska
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D020169:Caspases / Q000378:metabolism; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000494:pharmacology; D053200:Fas-Associated Death Domain Protein / Q000378:metabolism; D005260:Female; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D009944:Organoplatinum Compounds / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; C505533:FADD protein, human; D053200:Fas-Associated Death Domain Protein; D009944:Organoplatinum Compounds; C583242:Pt2(3-butylpyridine)4(berenil)2; C583243:Pt2(3-ethylpyridine)4(berenil)2; D020169:Caspases; D002945:Cisplatin