Evaluation of P53 and BAX gene expression and induction of apoptosis and necrosis by the cis-Pt(II) complex of 3-aminoflavone in comparison with cis-diamminedichloroplatinum(II) (cis-DDP) in human lymphocytes

被引:12
作者
Kosmider, B
Zawlik, I
Liberski, PP
Osiecka, R
Zyner, E
Ochocki, J
Bartkowiak, J
机构
[1] Texas A&M Univ, Syst Hlth Sci Ctr, Texas Med Ctr, Inst Biosci & Technol,Ctr Genome Res, Houston, TX 77030 USA
[2] Univ Lodz, Dept Cytogeet & Plant Mol Biol, PL-90237 Lodz, Poland
[3] Med Univ Lodz, Dept Mol Pathol & Neuropathol, Chair Oncol, PL-92216 Lodz, Poland
[4] Med Univ Lodz, Dept Bioinorgan Chem, PL-90151 Lodz, Poland
[5] Med Univ Lodz, Dept Med Biochem, PL-92215 Lodz, Poland
关键词
cis-Pt(II) complex of 3-aminoflavone; cis-DDP; apoptosis; necrosis; human lymphocytes;
D O I
10.1016/j.mrgentox.2005.12.006
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
Currently cis-diamminedichloroplatinum(H) (cis-DDP) is one of the most cornmonly applied compounds in chemotherapy of many types of cancer. However, a drawback is that its effectiveness presents with many side effects. Therefore, human normal lymphocytes were chosen as a model system to study cis-bis(3-aminoflavone)dichloroplatinum(II) (the cis-Pt(H) complex of 3-aminoflavone) in comparison with cis-DDP. We examined the effect of both tested compounds on cell viability and induction of apoptosis and necrosis. Trypan blue and acridine orange/ethidium bromide staining were carried out, as well as quantitative analysis of the apoptotic signal of P53 and BAX induction caused by the cis-Pt(III) complex of 3-aminoflavone in comparison with cis-DDP. cis-DDP induced a decrease of cell viability and led to a higher increase in necrosis and apoptosis than did the cis-Pt(II) complex of 3-aminoflavone. Moreover, at the molecular level cis-DDP increased P53 and BAX expression in comparison with the other tested compound. The cis-Pt(II) complex of 3-aminoflavone showed a weaker genotoxic effect in normal lymphocytes in comparison with cis-DDP, which was a stronger inducer of apoptosis and necrosis. (c) 2005 Elsevier B.V. All rights reserved.
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页码:28 / 35
页数:8
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