Korean J Physiol Pharmacol.
1997 Dec;1(6):817-824.
Apoptosis induced by adenosine 5'-trisphosphate in mouse leukemic
cells
- Affiliations
-
- 1
Department of Physiol., Yonsei University, Wonju Coll. Med., Wonju 220-701 South
Korea.
Abstract
-
Extracellular ATP elicits various biological responses and plays a
significant role in physiological regulation. Recently, ATP-induced
growth inhibitions were reported in some tumor cell lines, but these
effects and mechanisms are not well known. This study was conducted to
investigate ATP-induced growth inhibition in mouse leukemic (P388D,)
cells. ATP inhibited cell growth in a dose-dependent manner as analyzed
by MTS assay (IC50: 33.1 muM). Nucleotides other than ATP, such as ADP
(37.5 muM) and AMP (33.2 muM) had the same effects as ATP, but
adenosine (57.8 muM) showed less effect than ATP. ATP attenuated the
cells in G0/G1 and G2/M phases, but increased those in S phase in flow
cytometric analysis. Hypodiploid cells (A0), the presumptive findings
of apoptosis, were found among the ATP-treated cells. ATP induced DNA
fragmentation into 180 ~ 200 bps as measured by electrophoresis.
Some apoptotic cells were stained by TUNEL method. ATP increased the
intracellular free Ca++ concentration ((Ca++)i) and the increment of
(Ca++)i was caused by influx from the extracellular space. These
results
suggest that extracellular ATP induces growth inhibition
through apoptosis.