US EPA

1380630 

Journal Article 

Modulation of apoptosis signaling in etoposide-treated lymphoma cells 

Sebestyén, A; Mihalik, R; Peták, I; Kopper, L 

1997 

Yes 

Anticancer Research
ISSN: 0250-7005
EISSN: 1791-7530 

17 

4A 

2609-2614 

English 

9252689 

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.