Effect of extracellular ATP on breast tumor cell growth, implication of intracellular calcium.
We studied the effects of purine nucleotides and particularly adenosine triphosphate (ATP) in two (one hormonosensitive, MCF7 and one hormonoinsensitive, MDA-MB 231) human breast tumor cell lines. As described in other cells, we observed that purine nucleotides produced transient elevations in intracellular calcium ions, [Ca2+]i, in both types of cells as determined from Indo-1 fluorescence of loaded cells. In the absence of external calcium the [Ca2+]i transients consisted of single narrow peaks while an extension of peak duration along with a biphasic appearance were observed in the presence of external calcium. The potency of different purine nucleotides in elevating [Ca2+]i was ATP > ADP >> AMP > adenosine (which was inefficient) proving the presence of P2 purinergic receptor subtypes. Suramin, a compound known to compete with ATP for its binding sites, nearly abolished the effect of ATP on [Ca2+]i increase. while verapamil, a calcium channel blocker, was unable to abolish such an an ATP-induced [Ca2+]i increase. The concentrations of ATP required to increase [Ca2%bdi ranged from 10(-7) M to 10(-3) M, the maximal effect being obtained with 10(-4) M ATP. At this latter concentration, ATP induced cell growth inhibition which was dose-independent as triggered only when maximal elevation of [Ca2+]i was attained. This ATP concentration also induced maximal apoptotic features in both types of cells. Together, our results highlighted an 'all or none' effect of ATP on breast tumor cell growth mediated by its effect on [Ca2+]i liberation from intracellular stores, the first rise of [Ca2+]i being further amplified by an influx of calcium from extracellular space. The attainment of sufficient [Ca2+]i level then triggers cellular events.
Vandewalle
B
B
Laboratoire d'Endocrinologie Expérimentale, Centre Oscar Lambret, Lille, France.
Hornez
L
L
Revillion
F
F
Lefebvre
J
J
D000255:Adenosine Triphosphate / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology*; D002118:Calcium / Q000378:metabolism*; D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D006801:Humans; D007424:Intracellular Fluid / Q000378:metabolism; D007700:Kinetics; D009376:Neoplasms, Hormone-Dependent / Q000378:metabolism* / Q000473:pathology*; D011685:Purine Nucleotides / Q000494:pharmacology; D014407:Tumor Cells, Cultured / Q000187:drug effects
D011685:Purine Nucleotides; D000255:Adenosine Triphosphate; D002118:Calcium