Modulation of apoptosis signaling in etoposide-treated lymphoma cells.
Signals of etoposide (ETO) induced apoptosis were studied in a human (B) lymphoma cell line, HT58. Morphology and DNA fragmentation assays proved the appearance of apoptosis after a short ETO treatment (4 hours). Modulation of signal components of this apoptotic pathway resulted the following a) phorbol ester (PMA) or heat shock inhibited apoptosis, which was prevented by staurosporine b) 3-amino-benzamide, a potent poly(ADP-ribose)polymerase inhibitor, had no significant effect; c) cysteine reactive compounds, such as iodoacetamide and phenylarsine oxide, as well as protease inhibitor TPCK were very active inhibitors of apoptosis; d) protein synthesis inhibitor, cycloheximide, potentiated cell death; e) the ETO-induced p53 protein overexpression had neither enhancing nor protecting effect on the apoptotic process. In conclusion, in the majority of HT58 lymphoma cells the apoptotic machinery is "primed" (the components are already expressed) and ETO-induced apoptosis is regulated by STA sensitive phosphorylation and proteolysis by cystein proteases, but not affected by ADP-ribozylation or p53.
Sebestyén
A
A
Institute of Pathology and Experimental Cancer Research, Semmelweis University of Medicine, Budapest, Hungary.
Mihalik
R
R
Peták
I
I
Kopper
L
L
D017209:Apoptosis / Q000187:drug effects*; D001152:Arsenicals / Q000737:chemistry / Q000494:pharmacology; D003545:Cysteine / Q000737:chemistry; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D005047:Etoposide / Q000494:pharmacology*; D006358:Hot Temperature; D006801:Humans; D008228:Lymphoma, Non-Hodgkin / Q000473:pathology*; D010766:Phosphorylation; D011064:Poly Adenosine Diphosphate Ribose / Q000037:antagonists & inhibitors; D015398:Signal Transduction / Q000187:drug effects; D019311:Staurosporine / Q000494:pharmacology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects
D001152:Arsenicals; D015853:Cysteine Proteinase Inhibitors; D016159:Tumor Suppressor Protein p53; C029341:oxophenylarsine; D011064:Poly Adenosine Diphosphate Ribose; D005047:Etoposide; D019311:Staurosporine; D003545:Cysteine; D013755:Tetradecanoylphorbol Acetate