BCNU down-regulates anti-apoptotic proteins Bcl-xL and Bcl-2 in association with cell death in oligodendroglioma-derived cells

Richard A. Lytle, Zhihong Jiang, Xiao Zheng, Keith M. Rich

Research output: Contribution to journalArticle

20 Scopus citations

Abstract

Oligodendsroglial differentiation in gliomas is associated with enhanced sensitivity to chemotherapy. Anti-apoptotic proteins, Bcl-xL and Bcl-2, are over-expressed in early passage cell lines derived from glioblastomas. Down-regulation of Bcl-xL and Bcl-2 with DNA antisense oligonucleotides promotes cell death in glioblastoma cells. Changes of expression of Bcl-xL and Bcl-2 after chemotherapy treatment have not been studied in glioma subtypes. The current experiments correlate decreased expression of both Bcl-xL and Bcl-2 after BCNU chemotherapy and cell death in two oligodendroglioma-derived cell lines. Expression of Bcl-2 family member proteins Bcl-xL, Bcl-2, and Bax were assessed in glioma cells both before and after chemotherapy treatment. Cell survival was assessed with a crystal violet bioassay. Levels of expression of Bcl-2 and Bcl-xL were elevated in two early passage oligodendroglioma-derived cell lines compared with a non-neoplastic glial cell line. BCNU chemotherapy markedly down-regulated expression of Bcl-xL and Bcl-2 proteins in both oligodendroglioma-derived cell lines. Changes in expression of Bcl-xL and Bcl-2 were associated with the increased sensitivity to chemotherapy. There were no changes noted in expression of Bax after BCNU treatment. Modulation of expression of the anti-apoptotic proteins, Bcl-xL and Bcl-2, in the two oligodendroglioma-derived cell lines was associated with increased sensitivity to BCNU chemotherapy. Down-regulation of Bcl-xL and Bcl-2 resulted in reversal of the ratio of Bax/Bcl-xL and Bax/Bcl-2 and enhanced cell death after treatment with BCNU. Mechanisms that control expression of the anti-apoptotic proteins Bcl-xL and/or Bcl-2 may be effective targets in treatment strategies in patients with malignant gliomas.

Original languageEnglish
Pages (from-to)233-241
Number of pages9
JournalJournal of Neuro-Oncology
Volume68
Issue number3
DOIs
StatePublished - Jul 1 2004

Keywords

  • Apoptosis
  • Brain tumors
  • Cell death
  • Chemotheropy
  • Deamidation
  • Gliomas

Fingerprint Dive into the research topics of 'BCNU down-regulates anti-apoptotic proteins Bcl-xL and Bcl-2 in association with cell death in oligodendroglioma-derived cells'. Together they form a unique fingerprint.

  • Cite this