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

Risultato della ricerca: Article

5 Citazioni (Scopus)

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.
Lingua originaleEnglish
pagine (da-a)272-279
Numero di pagine8
RivistaChemotherapy
Volume51
Stato di pubblicazionePublished - 2005

Fingerprint

Inhibitor of Apoptosis Proteins
HL-60 Cells
Adenosine A3 Receptors
Adenosine
Leukemia
Apoptosis
Adenosine A3 Receptor Agonists
Messenger RNA
Phosphatidylserines
P-Glycoprotein
DNA Fragmentation
Verapamil
N(6)-(3-iodobenzyl)-5'-N-methylcarboxamidoadenosine
Anti-Idiotypic Antibodies
Flow Cytometry
Down-Regulation
Polymerase Chain Reaction
5'-N-methylcarboxamideadenosine

All Science Journal Classification (ASJC) codes

  • Oncology
  • Infectious Diseases
  • Pharmacology (medical)
  • Drug Discovery
  • Pharmacology

Cita questo

@article{e3b35254c07b4f5fae44fb7265667279,
title = "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",
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.",
keywords = "A 3 adenosine receptor, IB-MECA, Apoptosis, Multidrug resistance, Inhibitor of apoptosis proteins",
author = "Natale D'Alessandro and Maria Meli and Manuela Labbozzetta and {Notarbartolo Di Villarosa}, Monica and Paola Poma and Melchiorre Cervello",
year = "2005",
language = "English",
volume = "51",
pages = "272--279",
journal = "Chemotherapy",
issn = "0009-3157",
publisher = "S. Karger AG",

}

TY - JOUR

T1 - 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

AU - D'Alessandro, Natale

AU - Meli, Maria

AU - Labbozzetta, Manuela

AU - Notarbartolo Di Villarosa, Monica

AU - Poma, Paola

AU - Cervello, Melchiorre

PY - 2005

Y1 - 2005

N2 - 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.

AB - 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.

KW - A 3 adenosine receptor, IB-MECA, Apoptosis, Multidrug resistance, Inhibitor of apoptosis proteins

UR - http://hdl.handle.net/10447/21118

M3 - Article

VL - 51

SP - 272

EP - 279

JO - Chemotherapy

JF - Chemotherapy

SN - 0009-3157

ER -