Abstract
The mechanism by which Bcl-2 oncogene expression inhibits radiation-induced apoptosis has been investigated in two mouse lymphoma cell lines: line LY-as is radiation sensitive, displays substantial radiaton-induced apoptosis, and expresses low levels of Bcl-2; line LY-ar is radiation-resistant, displays a low apoptosis propensity, and expresses 30-fold higher amount of Bcl-2 protein than does the sensitive line. We observed that upon incubation in cystine/methionine-free (C/M-) medium, radiation-induced apoptosis in the LY-ar cells was restored to levels comparable to that seen in the LY-as cells. Intracellular glutathione (GSH) concentrations in LY-ar cells incubated in C/M- medium plummeted to 50% of control values within 2 h. LY-ar cells treated with diethyl maleate (DEM) or diamide, agents that deplete cellular thiols, had increased susceptibility to radiation-induced apoptosis in a manner similar to C/M- medium. These results are consistent with the general idea that Bcl-2 expression blocks apoptosis through an antioxidant pathway that involves cellular thiols. That Bcl-2-expressing tumor cells can be sensitized by exogeneous agents that modify cellular thiols offers strategies for overcoming such resistance.
Original language | English (US) |
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Pages (from-to) | 1461-1470 |
Number of pages | 10 |
Journal | Oncogene |
Volume | 15 |
Issue number | 12 |
DOIs | |
State | Published - 1997 |
Keywords
- Antioxidants
- Apoptosis
- Bcl-2
- Lymphoma
- Radiation
- Thiols
ASJC Scopus subject areas
- Molecular Biology
- Genetics
- Cancer Research