L-asparaginase kills lymphoma cells by apoptosis

Cancer Chemother Pharmacol. 1993;32(2):129-33. doi: 10.1007/BF00685615.

Abstract

Microscopic examination of histological sections of lymph nodes from a canine case of malignant lymphoma at 4 h after treatment with L-asparaginase revealed massive destruction of neoplastic cells by what was consistent with apoptosis morphologically. Apoptosis as the mode of cell death after asparaginase treatment was confirmed in a mouse lymphoma cell line (LY-TH) by the characteristic fragmentation of DNA into oligonucleosome-sized pieces and by the morphological changes consistent with apoptosis following treatment in vitro. Applied to these cells, asparaginase was found to be most cytotoxic over the range of 1-10 IU/ml. Even after 4 h of asparaginase treatment at 100 IU/ml, protein synthesis was reduced by only one-half, yet DNA fragmentation reached 40%. Other agents that affect protein synthesis (cycloheximide and actinomycin D) caused apoptosis as well; however, agents (radiation, prednisolone, and VP-16) whose mechanisms are different from inhibition of protein synthesis also caused apoptosis. As such, it seems unlikely that protein depletion per se and/or the elimination of specific short-lived proteins is the triggering event that leads to cell death. It is more likely that the suspension of cellular proliferation commits cells to apoptosis after asparaginase treatment.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Apoptosis / drug effects*
  • Asparaginase / pharmacology*
  • DNA, Neoplasm / drug effects
  • Dogs
  • Lymph Nodes / pathology
  • Lymphoma / pathology*
  • Lymphoma, B-Cell / pathology*
  • Male
  • Mice
  • Microscopy, Electron, Scanning
  • Neoplasm Proteins / biosynthesis
  • Tumor Cells, Cultured

Substances

  • DNA, Neoplasm
  • Neoplasm Proteins
  • Asparaginase