Variable susceptibility to apoptosis induced by calcium ionophore in hybridomas between HL-60 promyelocytic and CEM T-lymphoblastic leukemia cell lines: relationship to constitutive Mg(2+)-dependent endonuclease

Exp Cell Res. 1994 Aug;213(2):412-7. doi: 10.1006/excr.1994.1217.

Abstract

We recently reported that treatment with calcium ionophore, A23187, induces apoptosis in human myelogenous leukemia cells but causes necrotic cell death in T-lymphoblastic leukemia cells. To better understand the underlying mechanisms of such different modes of cell death, we established hybridomas between HL-60 promyelocytic and CEM T-lymphoblastic leukemia cells. The resulting hybridomas were divided into three groups in terms of their susceptibility to apoptosis following exposure to A23187: (1) hybridomas highly sensitive to apoptosis, (2) hybridomas with intermediate sensitivity to apoptosis which occurs later and to a lesser extent, and (3) hybridomas resistant to apoptosis. However, growth inhibition after 72 h of incubation and an initial rise in intracellular free calcium concentrations induced by A23187 were similar in the three groups. Expression of Ca(2+)-independent/Mg(2+)-dependent endonuclease, which had an optimal pH of 7.5-8.5 and was inhibited by Zn2+, was correlated with the susceptibility of the hybridomas to A23187-induced apoptosis. Thus, this endonuclease may play, at least in part, an important role in the induction of apoptosis in leukemia cell lines. Analysis of hybridomas between apoptosis-sensitive and apoptosis-resistant cells is useful in the elucidation of genetic factors which regulate cell death.

MeSH terms

  • Apoptosis*
  • Calcimycin / pharmacology*
  • Endonucleases / metabolism
  • Humans
  • Hybridomas / cytology*
  • Hybridomas / drug effects
  • Leukemia, Promyelocytic, Acute / metabolism*
  • Leukemia-Lymphoma, Adult T-Cell / metabolism*
  • Magnesium / metabolism
  • Tumor Cells, Cultured

Substances

  • Calcimycin
  • Endonucleases
  • Magnesium