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

Abstract：

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.

journal_name

Acta Pharmacol Sin

journal_title

Acta pharmacologica Sinica

authors

Li JY,Huang JY,Li M,Zhang H,Xing B,Chen G,Wei D,Gu PY,Hu WX

doi

10.1038/aps.2012.46

subject

Has Abstract

pub_date

2012-07-01 00:00:00

pages

935-40

issue

7

eissn

1671-4083

issn

1745-7254

pii

aps201246

journal_volume

33

pub_type

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