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Resistance to etoposide‐induced apoptosis in a Burkitt's lymphoma cell line
Author(s) -
Zhao E. G.,
Song Q.,
Cross S.,
Misko I.,
LeesMiller S. P.,
Lavin M. F.
Publication year - 1998
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/(sici)1097-0215(19980831)77:5<755::aid-ijc15>3.0.co;2-0
Subject(s) - burkitt's lymphoma , etoposide , apoptosis , lymphoma , cancer research , cell culture , medicine , biology , pathology , chemotherapy , genetics
Burkitt's lymphoma cells that vary in their phenotypic characteristics show significantly different degrees of susceptibility to radiation‐induced apoptosis. Propensity to undergo apoptosis is reflected in the degradation of substrates such as DNA‐dependent protein kinase but the status of bcl‐2, c‐myc and p53 has been uninformative. In this study, we have focused on 2 Epstein‐Barr virus (EBV)‐associated Burkitt's cell lines, one (WW2) susceptible and the other (BL29) resistant to etoposide‐induced apoptosis. Differences in expression of BHRF 1, an EBV gene that is homologous to the Bcl ‐2 proto‐oncogene and known to inhibit apoptosis, or changes in apoptosis inhibitory proteins (IAPs), did not appear to account for the difference in susceptibility in the 2 cell lines. Cytoplasmic extracts from etoposide‐treated WW2 cells caused apoptotic changes in nuclei isolated from either BL29 or WW2 cells, whereas extracts from BL29 cells failed to do so. In addition, extracts from etoposide‐treated WW2 cells degraded the catalytic subunit of DNA‐dependent protein kinase (DNA‐PKcs), an important indicator of apoptosis, but this protein was resistant to degradation by BL29 extracts. It appears likely that caspase 3 (CPP32) is involved in this degradation since it was activated only in the apoptosis susceptible cells and the pattern of cleavage of DNA‐PKcs was similar to that reported previously with recombinant caspase 3. As observed previously, addition of caspase 3 to nuclei failed to induce morphological changes indicative of apoptosis, but addition of caspase 3 to nuclei in the presence of extract from the resistant cells led to apoptotic changes. We conclude that resistance to apoptosis in BL29 cells is due to a failure of etoposide to activate upstream effectors of caspase activity. Int. J. Cancer 77:755–762, 1998. © 1998 Wiley‐Liss, Inc.