Neoplasma Vol.60, No.1, p.101-110, 2013
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| Title: Anisomycin Induces Apoptosis of Glucocorticoid Resistant Acute Lymphoblastic Leukemia CEM-C1 Cells via Activation of Mitogen-Activated Protein Kinases p38 and JNK |
| Author: Y. LIU, J. GE, Q. LI, L. GU, X. GUO, Z. G. MA, Y. P. ZHU |
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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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| Keywords: anisomycin, acute lymphoblastic leukemia (ALL), glucocorticoid resistance, apoptosis, p38-Mitogen-Activated Protein Kinases (p-38MAPKs), Jun N-terminal kinase (JNK) |
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| Year: 2013, Volume: 60, Issue: 1 |
Page From: 101, Page To: 110 |
doi:10.4149/neo_2013_014
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