Antisense BAG-1 sensitizes HeLa cells to apoptosis by multiple pathways

Jieying Xiong, Jun Chen, Garry Chernenko, Jessalyn Beck, Hongyu Liu, Alan Pater, Shou-Ching Tang

Research output: Contribution to journalArticlepeer-review

20 Scopus citations

Abstract

To study the mechanism of action of BAG-1 in drug-induced apoptosis, we constructed an antisense BAG-1 vector and established a stably transfected cell line from BAG-1-over-expressing HeLa cells. Reduced BAG-1 protein was confirmed by Western blot. Treatment of the antisense BAG-1-transfected cells with the anti-cancer drugs staurosporine, paclitaxel, all-trans retinoic acid (ATRA), and N-(4-hydroxyphenyl) retinamide (4-HPR) resulted in significantly enhanced apoptosis and reduced cell viability relative to vector-transfected cells. While the expression of p53 was increased, the level of Bcl-2 and Bax was decreased. Cells underexpressing BAG-1 had reduced cytosolic cytochrome c level. Treatment with staurosporine and paclitaxel resulted in increased cytochrome c release from mitochondria, whereas there was no change induced by treatment with ATRA and 4-HPR. Our experiments suggest that BAG-1 inhibits anti-cancer drug-induced apoptosis through apoptosis regulation pathways that may involve the mitochondrial Bcl-2/Bax ratio, p53, and differential anti-cancer drug-mediated cytochrome c release.

Original languageEnglish (US)
Pages (from-to)585-591
Number of pages7
JournalBiochemical and Biophysical Research Communications
Volume312
Issue number3
DOIs
StatePublished - Dec 19 2003

Keywords

  • Antisense down-regulation
  • Apoptosis
  • BAG-1
  • Bcl-2 apoptotic family
  • Mitochondrial pathway
  • p53

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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