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.
Currently cis-diamminedichloroplatinum(II) (cis-DDP) is one of the most commonly 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(II) 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(II) 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.
Kosmider
Beata
B
Department of Cytogenetics and Plant Molecular Biology, University of Lodz, Banacha 12/16, 90-237 Lodz, Poland. beatakosmider@interia.pl
Zawlik
Izabela
I
Liberski
Pawel P
PP
Osiecka
Regina
R
Zyner
Elzbieta
E
Ochocki
Justyn
J
Bartkowiak
Jacek
J
D017209:Apoptosis / Q000187:drug effects*; D001483:Base Sequence; D018929:Cell Culture Techniques; D002470:Cell Survival / Q000187:drug effects; D002945:Cisplatin / Q000633:toxicity*; D017931:DNA Primers; D005419:Flavonoids / Q000633:toxicity*; D005786:Gene Expression Regulation / Q000187:drug effects*; D016158:Genes, p53 / Q000187:drug effects*; D006801:Humans; D008214:Lymphocytes / Q000166:cytology* / Q000187:drug effects / Q000502:physiology; D009336:Necrosis; D012333:RNA, Messenger / Q000235:genetics; D051028:bcl-2-Associated X Protein / Q000187:drug effects / Q000235:genetics*
C488624:3-aminoflavone; D017931:DNA Primers; D005419:Flavonoids; D012333:RNA, Messenger; D051028:bcl-2-Associated X Protein; D002945:Cisplatin