Resistance to radiation-induced apoptosis in Bcl-2-expressing cells is reversed by depleting cellular thiols

Nena Mirkovic, David W. Voehringer, Michael D. Story, David J. McConkey, Timothy J. McDonnell, Raymond E. Meyn

Research output: Contribution to journalArticle

200 Citations (Scopus)

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 languageEnglish (US)
Pages (from-to)1461-1470
Number of pages10
JournalOncogene
Volume15
Issue number12
StatePublished - 1997

Fingerprint

Sulfhydryl Compounds
Radiation
Apoptosis
Cystine
Methionine
diethyl maleate
Diamide
Oncogenes
Glutathione
Lymphoma
Antioxidants
Cell Line
Neoplasms
Proteins

Keywords

  • Antioxidants
  • Apoptosis
  • Bcl-2
  • Lymphoma
  • Radiation
  • Thiols

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research
  • Genetics

Cite this

Mirkovic, N., Voehringer, D. W., Story, M. D., McConkey, D. J., McDonnell, T. J., & Meyn, R. E. (1997). Resistance to radiation-induced apoptosis in Bcl-2-expressing cells is reversed by depleting cellular thiols. Oncogene, 15(12), 1461-1470.

Resistance to radiation-induced apoptosis in Bcl-2-expressing cells is reversed by depleting cellular thiols. / Mirkovic, Nena; Voehringer, David W.; Story, Michael D.; McConkey, David J.; McDonnell, Timothy J.; Meyn, Raymond E.

In: Oncogene, Vol. 15, No. 12, 1997, p. 1461-1470.

Research output: Contribution to journalArticle

Mirkovic, N, Voehringer, DW, Story, MD, McConkey, DJ, McDonnell, TJ & Meyn, RE 1997, 'Resistance to radiation-induced apoptosis in Bcl-2-expressing cells is reversed by depleting cellular thiols', Oncogene, vol. 15, no. 12, pp. 1461-1470.
Mirkovic N, Voehringer DW, Story MD, McConkey DJ, McDonnell TJ, Meyn RE. Resistance to radiation-induced apoptosis in Bcl-2-expressing cells is reversed by depleting cellular thiols. Oncogene. 1997;15(12):1461-1470.
Mirkovic, Nena ; Voehringer, David W. ; Story, Michael D. ; McConkey, David J. ; McDonnell, Timothy J. ; Meyn, Raymond E. / Resistance to radiation-induced apoptosis in Bcl-2-expressing cells is reversed by depleting cellular thiols. In: Oncogene. 1997 ; Vol. 15, No. 12. pp. 1461-1470.
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