Abstract |
Glucocorticoids (GCs) resistance is frequently encountered in children with acute lymphoblastic leukemia (ALL), especially in T-ALL, which usually results in failure of treatment. To find new agent to overcome GC resistance of ALL is an urgent problem. Here we investigated potential effect of anisomycin on GC-resistant T-ALL CEM-C1 cells and explored involved molecular mechanisms. Dramatic growth inhibition and apoptosis in GC resistant CEM-C1 cells and GC-sensitive CEM-C7 cells induced by anisomycin were observed, which presented in a concentration- and time-dependent manner. Correspondingly, anisomycin induced cleaved caspase-3 and up-regulation of pro-apoptotic proteins (BimEL and Bad), meanwhile down-regulation of anti-apoptotic proteins (Mcl-1 and Bcl-2), both in a dose- and time-dependent manner in GC resistant CEM-C1 cells. Anisomycin also induced cell cycle arrest at G0/G1 phase in CEM-C1 cells through increasing expressions of p21 and p27, and attenuating the expression of cyclinA. The rapid up-regulation of phosphorylated mitogen-activated protein kinases (MAPKs) p38 and Jun N-terminal kinase (JNK) were observed after CEM-C1 cells were incubated with anisomycin. The activation of p38 and JNK could be blocked by respective inhibitors ( SB203580 for p38 and SP600125 for JNK) accompanied with the inhibition of apoptosis and changes of apoptosis associated proteins in CEM-C1 cells. These results suggested that anisomycin induced apoptosis of CEM-C1 cells via activation of p38 and JNK, and might be an attractive new agent for treatment of GC-resistant ALL.
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Authors | Y Liu, J Ge, Q Li, L Gu, X Guo, Z G Ma, Y P Zhu |
Journal | Neoplasma
(Neoplasma)
Vol. 60
Issue 1
Pg. 101-10
( 2013)
ISSN: 0028-2685 [Print] Slovakia |
PMID | 23067223
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Antineoplastic Agents, Hormonal
- Nucleic Acid Synthesis Inhibitors
- RNA, Messenger
- Anisomycin
- Dexamethasone
- JNK Mitogen-Activated Protein Kinases
- p38 Mitogen-Activated Protein Kinases
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Topics |
- Anisomycin
(pharmacology)
- Antineoplastic Agents, Hormonal
(pharmacology)
- Apoptosis
(drug effects)
- Blotting, Western
- Cell Proliferation
(drug effects)
- Dexamethasone
(pharmacology)
- Drug Resistance, Neoplasm
(drug effects)
- Flow Cytometry
- Humans
- JNK Mitogen-Activated Protein Kinases
(metabolism)
- Nucleic Acid Synthesis Inhibitors
(pharmacology)
- Phosphorylation
(drug effects)
- Precursor Cell Lymphoblastic Leukemia-Lymphoma
(drug therapy, metabolism, pathology)
- RNA, Messenger
(genetics)
- Signal Transduction
- Tumor Cells, Cultured
- p38 Mitogen-Activated Protein Kinases
(metabolism)
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