Bmf is upregulated by PS-341-mediated cell death of glioma cells through JNK phosphorylation

Mol Biol Rep. 2010 Mar;37(3):1211-9. doi: 10.1007/s11033-009-9491-9. Epub 2009 Mar 7.

Abstract

Malignant glioma is resistant to the induction of apoptosis, resulting in a subsequent failure of chemotherapy in clinical treatment strategies. Downregulation of bcl-2 and bcl-xl expression in glioblastoma cells can induce apoptosis. BH3-only proteins, which include Bmf, are essential initiators of stress-induced cell death and apoptosis. Whether PS-341 regulates expression of BH3-only proteins in glioblastoma cells during the procedure of apoptosis is unclear. This study was designed to investigate the effects of PS-341 on glioma cell death and its possible signaling pathway. Our results demonstrate that Bmf is upregulated by PS-341 in A172 and T98G cells, and Bmf has a crucial role in PS-341-mediated cell death. In addition, we found that expression of Bmf is regulated by JNK phosphorylation.

MeSH terms

  • Adaptor Proteins, Signal Transducing / metabolism*
  • Analysis of Variance
  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects*
  • Blotting, Western
  • Boronic Acids / pharmacology*
  • Bortezomib
  • Cell Line, Tumor
  • DNA Fragmentation
  • Flow Cytometry
  • Gene Expression Regulation, Neoplastic / drug effects*
  • Glioma / metabolism*
  • Humans
  • MAP Kinase Kinase 4 / metabolism
  • Phosphorylation
  • Pyrazines / pharmacology*
  • RNA, Small Interfering / genetics
  • Reverse Transcriptase Polymerase Chain Reaction
  • Signal Transduction / drug effects*
  • Tetrazolium Salts
  • Thiazoles

Substances

  • Adaptor Proteins, Signal Transducing
  • Antineoplastic Agents
  • BMF protein, human
  • Boronic Acids
  • Pyrazines
  • RNA, Small Interfering
  • Tetrazolium Salts
  • Thiazoles
  • Bortezomib
  • MAP Kinase Kinase 4
  • thiazolyl blue