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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.

Abstract
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.
AuthorsBeata Kosmider, Izabela Zawlik, Pawel P Liberski, Regina Osiecka, Elzbieta Zyner, Justyn Ochocki, Jacek Bartkowiak
JournalMutation research (Mutat Res) Vol. 604 Issue 1-2 Pg. 28-35 (Apr 30 2006) ISSN: 0027-5107 [Print] Netherlands
PMID16443387 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • 3-aminoflavone
  • DNA Primers
  • Flavonoids
  • RNA, Messenger
  • bcl-2-Associated X Protein
  • Cisplatin
Topics
  • Apoptosis (drug effects)
  • Base Sequence
  • Cell Culture Techniques
  • Cell Survival (drug effects)
  • Cisplatin (toxicity)
  • DNA Primers
  • Flavonoids (toxicity)
  • Gene Expression Regulation (drug effects)
  • Genes, p53 (drug effects)
  • Humans
  • Lymphocytes (cytology, drug effects, physiology)
  • Necrosis
  • RNA, Messenger (genetics)
  • bcl-2-Associated X Protein (drug effects, genetics)

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