Apoptosis induction in lymphoma cells: thiol deprivation versus thiol excess.
We studied the effects of thiol availability on apoptosis induction in B-cell lymphoma 38C13, T-cell lymphoma EL4, and also other cells. Compounds with a free SH group are required for survival and growth of 38C13 cells but not of EL4 cells. Thiol deprivation (2-mercaptoethanol concentrations about 0.3 microM and lower) induced apoptosis in 38C13 cells. On the other hand, thiol excess (2-mercaptoethanol concentrations higher than 300 microM) induced apoptosis in 38C13 cells and EL4 cells as well as in other cells (e.g. Raji, HeLa). L-cystine and non-thiol antioxidant ascorbic acid were unable to support survival of 38C13 cells. Ascorbic acid induced cell death at concentrations higher than 600 microM. Thiol cross-linking compound diamide (100 microM and higher) abrogated the survival-supporting effect of 2-mercaptoethanol (50 microM). Apoptosis induction by thiol deprivation and by thiol excess was not directly related to a specific significant change in the p53 level or p53 activation. Apoptosis induction by thiol excess was associated with a certain decrease in the Bcl-2 level while the Bax level did not change. We conclude that both thiol deprivation and thiol excess can induce apoptosis in lymphoma cells. Apoptosis induction by thiol deprivation is specifically related to the presence of a free SH group. However, apoptosis induction by thiol excess does not seem to be specifically related to the presence of a free SH group. It probably results from the excess of a reductant. Apoptotic control protein p53 does not seem to play a significant role in apoptosis induction either by thiol deprivation or by thiol excess.
Kovár
J
J
Institute of Molecular Genetics, Academy of Sciences of the Czech Republic, Prague. kovar@biomed.cas.cz
Stýbrová
H
H
Truksa
J
J
Spĕváková
K
K
Valenta
T
T
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002453:Cell Cycle / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006367:HeLa Cells; D006801:Humans; D008223:Lymphoma / Q000473:pathology*; D016393:Lymphoma, B-Cell / Q000473:pathology; D016399:Lymphoma, T-Cell / Q000473:pathology; D008623:Mercaptoethanol / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology; D051379:Mice; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D013438:Sulfhydryl Compounds / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D051028:bcl-2-Associated X Protein
C494826:BAX protein, human; C494827:Bax protein, mouse; C493956:CDKN1A protein, human; C493957:Cdkn1a protein, mouse; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D013438:Sulfhydryl Compounds; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein; D008623:Mercaptoethanol