Bcl-xl antisense treatment induces apoptosis in breast carcinoma cells

Int J Cancer. 2000 Aug 15;87(4):582-90. doi: 10.1002/1097-0215(20000815)87:4<582::aid-ijc19>3.0.co;2-p.


Upregulated expression of bcl-xL is involved in the initiation and progression of breast cancer by inhibiting tumor cell apoptosis. Here we describe the use of the 2;-O-methoxy-ethoxy antisense oligonucleotide 4259 targeting nucleotides 687-706 of the bcl-xL mRNA, a sequence that does not occur in the pro-apoptotic bcl-xS transcript, to restore apoptosis in estrogen-dependent and independent breast carcinoma cells. The antisense effect of oligonucleotide 4259 was examined on the mRNA and protein level using real-time PCR and Western blot analysis, respectively, and the induction of cell death was investigated in viability and apoptosis assays. Treatment of MCF7 cells with oligonucleotide 4259 at a concentration of 600 nM for 20 hr decreased bcl-xL mRNA and protein levels by more than 80% and 50%, respectively. This resulted in the induction of apoptosis characterized by mitochondrial cytochrome c release, decrease of mitochondrial transmembrane potential, and the appearance of condensed nuclei in approximately 40% of cells. Moreover, oligonucleotide 4259 efficiently downregulated bcl-xL expression and decreased cell growth in the breast carcinoma cell lines T-47D, ZR-75-1, and MDA-MB-231. Our data emphasize the importance of bcl-xL as a survival factor for breast carcinoma cells and suggest that oligonucleotide 4259 deserves further investigations for use in breast cancer therapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / drug effects*
  • Apoptosis / physiology
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology*
  • Cell Death / drug effects
  • Cell Death / physiology
  • Cell Division / drug effects
  • Cell Survival / drug effects
  • Down-Regulation
  • Estrogens / physiology
  • Humans
  • Neoplasms, Hormone-Dependent / pathology
  • Oligonucleotides, Antisense / genetics
  • Oligonucleotides, Antisense / pharmacology*
  • Proto-Oncogene Proteins c-bcl-2 / biosynthesis
  • Proto-Oncogene Proteins c-bcl-2 / genetics*
  • Proto-Oncogene Proteins c-bcl-2 / physiology
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Signal Transduction / drug effects
  • Signal Transduction / physiology
  • Tumor Cells, Cultured / drug effects
  • bcl-X Protein


  • BCL2L1 protein, human
  • Estrogens
  • Oligonucleotides, Antisense
  • Proto-Oncogene Proteins c-bcl-2
  • RNA, Messenger
  • bcl-X Protein