Modulation of apoptosis and enhancement of chemosensitivity by decreasing cellular thiois in a mouse B-cell lymphoma cell line that overexpresses bcl-2

Michael D. Story, Raymond E. Meyn

Research output: Contribution to journalArticle

12 Scopus citations

Abstract

Purpose: To determine whether the difference in the apoptosis and clonogenic survival responses to radiation observed between the murine lymphoma cell lines LY-ar, which expresses bcl-2, and LY-as, which does not, was also evident after treatment with chemotherapy agents; and to determine whether clonogenie survival after chemotherapy agent exposure could be diminished by enhancing apoptosis through a decrease in cellular thiols. Methods: Cells were treated with cisplatin, VP-16, or Adriamycin, and apoptosis was determined using a DNA fragmentation assay. Cellular survival was quantified by limiting dilution assay. Intracellular thiols were decreased by maintaining LY-ar cells in cystine/methionine-free medium (CMF medium) for 7 h after drug treatment. Results: LY-as cells were approximately four times more likely to undergo apoptosis than LY-ar cells, having differences in apoptosis of 80% and 20%, respectively, for the agents used. LY-as cells were also more sensitive as measured by cellular survival, with a dose-modifying factor of about 1.8 measured at a 10% survival level. Incubation of LY-ar cells in CMF medium after drug treatment increased apoptosis and reduced clonogenic survival to the levels seen in LY-as cells, except after treatment with VP-16, where the reduction in cell survival was more modest. Conclusions: Decreasing intracellular thiols enhances apoptosis and cell killing in lymphoma cells after exposure to a variety of chemotherapy agents. This may be especially true for tumor cells that overexpress bcl-2, a gene that modifies cellular thiol status and conveys resistance to apoptosis. In this case, decreasing cellular thiols allows killing independent of the expression of bcl-2.

Original languageEnglish (US)
Pages (from-to)362-366
Number of pages5
JournalCancer Chemotherapy and Pharmacology
Volume44
Issue number5
DOIs
StatePublished - Oct 7 1999

Keywords

  • Adriamycin
  • Apoptosis
  • Bcl-2
  • Cisplatin
  • Thiols

ASJC Scopus subject areas

  • Oncology
  • Toxicology
  • Pharmacology
  • Cancer Research
  • Pharmacology (medical)

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