Apoptosis Induced by Adenosine 5'-triphosphate in Mouse Leukemic Cells

Mouse Leukemia 세포에서 Adenosine 5'-triphosphate에 의한 Apoptosis

  • Joo, Nan-Young (Department of Physiology, Yonsei University Wonju College of Medicine) ;
  • Park, Kyu-Sang (Department of Physiology, Yonsei University Wonju College of Medicine) ;
  • Chung, Hae-Sook (Department of Physiology, Yonsei University Wonju College of Medicine) ;
  • Kong, In-Deok (Department of Physiology, Yonsei University Wonju College of Medicine) ;
  • Lee, Joong-Woo (Department of Physiology, Yonsei University Wonju College of Medicine)
  • 주난영 (연세대학교 원주의과대학 생리학교실) ;
  • 박규상 (연세대학교 원주의과대학 생리학교실) ;
  • 정해숙 (연세대학교 원주의과대학 생리학교실) ;
  • 공인덕 (연세대학교 원주의과대학 생리학교실) ;
  • 이중우 (연세대학교 원주의과대학 생리학교실)
  • Published : 1997.12.21

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 hewn. This study was conducted to investigate ATP-induced growth inhibition in mouse $leukemic(P388D_1)$ cells. ATP inhibited cell growth in a dose-dependent manner as analyzed by MTS assay$(IC_{50}: 33.1\;{\mu}M)$. Nucleotides other than ATP, such as ADP$(37.5;{\mu}M)$ and AMP$(33.2;{\mu}M)$ had the same effects as ATP but adenosine$(57.8;{\mu}M)$ showed less effect than ATP. ATP attenuated the cells in $G_0/G_l\;and\;G_2/M$ phases but increased those in S phase in flow cytometric analysis. Hypodiploid cells$(A_0)$, the presumptive findings of apoptosis, were found among the ATP-treated cells. ATP induced DNA fragmentation into $180{\mu}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.