L-asparaginase kills lymphoma cells by apoptosis.
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.
Story
M D
MD
Department of Experimental Radiotherapy, University of Texas M.D. Anderson Cancer Center, Houston 77030.
Voehringer
D W
DW
Stephens
L C
LC
Meyn
R E
RE
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001215:Asparaginase / Q000494:pharmacology*; D004273:DNA, Neoplasm / Q000187:drug effects; D004285:Dogs; D008198:Lymph Nodes / Q000473:pathology; D008223:Lymphoma / Q000473:pathology*; D016393:Lymphoma, B-Cell / Q000473:pathology*; D008297:Male; D051379:Mice; D008855:Microscopy, Electron, Scanning; D009363:Neoplasm Proteins / Q000096:biosynthesis; D014407:Tumor Cells, Cultured
D004273:DNA, Neoplasm; D009363:Neoplasm Proteins; D001215:Asparaginase