Effect of Extracellular ATP on the Human Leukaemic Cell Line K562 and its Multidrug Counterpart

Extracellular ATP (ATPo) is capable of inducing different events on cells through receptor activation. The effect produced by ATPo was studied in the cell line K562 and its multidrug resistant (MDR) counterpart, Lucena 1. Lower ATPo concentrations (1 mM and 2.5 mM) led to high ³H-thymidine incorpora...

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Bibliographic Details
Published in:Molecular and cellular biochemistry 2006-09, Vol.289 (1-2), p.111-124
Main Authors: Bernardo, Alcira A, Pinto-Silva, Flavio Eduardo, Persechini, Pedro M, Coutinho-Silva, Robson, Meyer-Fernandes, José Roberto, Souza, André Luiz Fonseca de, Rumjanek, Vivian M
Format: Article
Language:English
Subjects:
5'-Nucleotidase - metabolism
Adenosine - pharmacology
Adenosine Triphosphatases - metabolism
Adenosine Triphosphate - pharmacology
Apoptosis
Apoptosis - drug effects
Apyrase - metabolism
ATP-Binding Cassette, Sub-Family B, Member 1 - metabolism
Cell cycle
Cell Cycle - drug effects
Cell Membrane Permeability - drug effects
Cell Survival - drug effects
Drug Resistance, Multiple - drug effects
ecto-5'nucleotidase
ecto-ATPase
extracellular ATP
Humans
K562 Cells
Kinetics
leukaemias
multiple drug resistance
Phenotype
Protein Binding - drug effects
Proteins
Purinergic P2 Receptor Agonists
Purinergic P2 Receptor Antagonists
Receptors, Purinergic P2X7
Thymidine - biosynthesis
Tritium
Tumor Cells, Cultured
Uridine Triphosphate - pharmacology
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Summary:Extracellular ATP (ATPo) is capable of inducing different events on cells through receptor activation. The effect produced by ATPo was studied in the cell line K562 and its multidrug resistant (MDR) counterpart, Lucena 1. Lower ATPo concentrations (1 mM and 2.5 mM) led to high ³H-thymidine incorporation but no increase in cell number. Similarly, the cell cycle profile indicated an increase of cells in S phase and a decrease in G1 and G2, suggesting that the cells did not duplicate their DNA content. Higher doses of ATP (5 mM and 10 mM), as well as UTP (5 mM) and the P2X₇ agonist BzATP, were cytotoxic. However, no expression of P2X₇ receptors could be detected by Western Blot nor were the cells permeabilised by ATP, suggesting that pore formation was not involved in cell death. Both ecto-ATPase and ecto-5'-nucleotidase activity could be demonstrated at the surfaces of K562 and Lucena 1 cells, the latter presenting a higher ecto-5'-nucleotidase activity. Adenosine induced cell death at lower concentrations (2.5 mM) on both cell lines. Furthermore, an increased number of dead cells could be observed when 5 mM Adenosine was used compared to the same concentrations of ATPo. It still remains to be elucidated the nature of the receptors involved in the induction of cell death in these cells.
ISSN:0300-8177
1573-4919
DOI:10.1007/s11010-006-9154-2