Enhanced P53 and BAX gene expression and apoptosis in A549 cells by cis-Pt(II) complex of 3-aminoflavone in comparison with cis-DDP.
Lung cancer remains one of the most common causes of cancer-related death worldwide. Approximately 80% is histologically non-small cell lung carcinoma (NSCLC) and in about 70% of patients it is an unresectable type. Clinical studies indicated that application of platinum derivatives caused good results and combinations of platinum with other agents could improve median survivals. In view of the central problem of sufficient efficiency of drugs in chemotherapy, efforts have focused on the development of alternative platinum-based analogues that can be more effective in cancer treatment. cis-bis(3-aminoflavone)dichloroplatinum(II) (cis-Pt(II) complex of 3-aminoflavone) represents a novel class of platinum-based potential antitumour agents. In order to evaluate the degree of apoptosis, acridine orange/ethidium bromide and Hoechst 33258/propidum iodide double staining as well as RT-PCR (P53 and BAX expression evaluation) were used in lung cancer cell line A549 after treatment with this compound in comparison with cis-diamminedichloroplatinum(II) (cis-DDP). Apoptotic cells at early and late stages and also necrotic ones were observed after usage of cis-Pt(II) complex of 3-aminoflavone and the percentage of these cells outnumbered the values obtained after cis-DDP application. The former compound induced a higher percentage of P53 and BAX expression in A549 cells in comparison with the latter one. Results indicate the beneficial properties of cis-Pt(II) complex of 3-aminoflavone as a potential antitumor drug.
Kosmider
Beata
B
Department of Cytogenetics and Plant Molecular Biology, University of Lodz, ul. Banacha 12/16, 90-237 Lodz, Poland. beatakosmider@interia.pl
Wojcik
Izabela
I
Osiecka
Regina
R
Bartkowiak
Jacek
J
Zyner
Elzbieta
E
Ochocki
Justyn
J
Liberski
Pawel
P
D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D009944:Organoplatinum Compounds / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D013997:Time Factors; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D051028:bcl-2-Associated X Protein / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*
D000970:Antineoplastic Agents; D009944:Organoplatinum Compounds; D012333:RNA, Messenger; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein; C488623:cis-bis(3-aminoflavone)dichloroplatinum(II); D002945:Cisplatin