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MARIA MELI

Induction of apoptosis by the adenosine derivative IB-MECA in parental or multidrug-resistant HL-60 leukemia cells: possibile relationship to the effects on inhibitor of apoptosis protein levels

  • Autori: NOTARBARTOLO DI VILLAROSA, M.; LO CICERO, S.; Meli, M.; Poma, P.; Labbozzetta, M.; Cervello, M.; D'Alessandro, N.
  • Anno di pubblicazione: 2005
  • Tipologia: Articolo in rivista (Articolo in rivista)
  • Parole Chiave: A 3 adenosine receptor, IB-MECA, Apoptosis, Multidrug resistance, Inhibitor of apoptosis proteins
  • OA Link: http://hdl.handle.net/10447/21118

Abstract

Background: The effects of the A3 adenosine receptor (A3AR) agonist lB-MECA were examined in HL-60 leukemia and in its multidrug-resistant variant HL60R cells. Methods: Cytotoxicity was evaluated by MTS assays and apoptosis by flow cytometry analyses of DNA fragmentation and phosphatidylserine exposure. The mRNAs of A3AR and inhlbitor of apoptosis proteins (lAPs) were determined by RT-PCR. Results: A3AR expression was similar in HL-60 and HL-60R cells. At ≥ 100 μM, IB-MECA exhibited strong cytotoxic and apoptotic effects in HL-60, but not in HL-60R cells. This activity was not modified by the A3AR antagonis VUF5574, the P-glycoprotein inhibitor verapamil, the adenosine uptake inhibitor NBTI or the anti Fas antibody Z B4, HL-60R cells showed higher levels of different IAPs than H L-60 cells. lB-MECA 100 μM downregulated HlAP1, NAIP and survivin mRNAs in HL-60, but not in HL-60R cells. Conclusions: The antitumor effects of IB-MECA are not mediated by A3AR in HL-60 cells, where the proapoptotic mechanism of the compound may involve downregulation of lAPs. The resistance of HL-60R cells to lB-MECA may depend on their elevated levels of lAPs.