Literature DB >> 22684030

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

Jun-yang Li1, Jia-yuan Huang, Meng Li, Han Zhang, Biao Xing, Gong Chen, Dong Wei, Pei-yuan Gu, Wei-xing Hu.   

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.

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Year:  2012        PMID: 22684030      PMCID: PMC4011155          DOI: 10.1038/aps.2012.46

Source DB:  PubMed          Journal:  Acta Pharmacol Sin        ISSN: 1671-4083            Impact factor:   6.150


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