Anisomycin induces glioma cell death via down-regulation of PP2A catalytic subunit in vitro

Acta Pharmacol Sin. 2012 Jul;33(7):935-40. doi: 10.1038/aps.2012.46. Epub 2012 Jun 11.


Aim: To examine the effects of anisomycin on glioma cells and the related mechanisms in vitro.

Methods: The U251 and U87 human glioblastoma cell lines were tested. The growth of the cells was analyzed using a CCK-8 cell viability assay. Apoptosis was detected using a flow cytometry assay. The expression of proteins and phosphorylated kinases was detected using Western blotting.

Results: Treatment of U251 and U87 cells with anisomycin (0.01-8 μmol/L) inhibited the cell growth in time- and concentration-dependent manners (the IC(50) values at 48 h were 0.233±0.021 and 0.192±0.018 μmol/L, respectively). Anisomycin (4 μmol/L) caused 21.5%±2.2% and 25.3%±3.1% of apoptosis proportion, respectively, in U251 and U87 cells. In the two cell lines, anisomycin (4 μmol/L) activated p38 MAPK and JNK, and inactivated ERK1/2. However, neither the p38 MAPK inhibitor SB203580 (10 μmol/L) nor the JNK inhibitor SP600125 (10 μmol/L) prevented anisomycin-induced cell death. On the other hand, anisomycin (4 μmol/L) reduced the level of PP2A/C subunit (catalytic subunit) in a time-dependent manner in the two cell lines. Treatment of the two cell lines with the PP2A inhibitor okadaic acid (100 nmol/L) caused marked cell death.

Conclusion: Anisomycin induces glioma cell death via down-regulation of PP2A catalytic subunit. The regulation of PP2A/C exression by anisomycin provides a clue to further study on its role in glioma therapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anisomycin / pharmacology*
  • Anti-Bacterial Agents / pharmacology*
  • Apoptosis / drug effects
  • Cell Death / drug effects
  • Cell Line, Tumor
  • Down-Regulation / drug effects*
  • Enzyme Activation / drug effects
  • Glioblastoma / drug therapy*
  • Glioblastoma / genetics
  • Glioblastoma / metabolism
  • Humans
  • JNK Mitogen-Activated Protein Kinases / antagonists & inhibitors
  • JNK Mitogen-Activated Protein Kinases / metabolism
  • Mitogen-Activated Protein Kinase 1 / metabolism
  • Mitogen-Activated Protein Kinase 3 / metabolism
  • Protein Phosphatase 2 / genetics*
  • Protein Subunits / genetics
  • Protein Synthesis Inhibitors / pharmacology*
  • p38 Mitogen-Activated Protein Kinases / antagonists & inhibitors
  • p38 Mitogen-Activated Protein Kinases / metabolism


  • Anti-Bacterial Agents
  • Protein Subunits
  • Protein Synthesis Inhibitors
  • Anisomycin
  • JNK Mitogen-Activated Protein Kinases
  • Mitogen-Activated Protein Kinase 1
  • Mitogen-Activated Protein Kinase 3
  • p38 Mitogen-Activated Protein Kinases
  • PPP2CA protein, human
  • Protein Phosphatase 2