BMS-345541 induces apoptosis of glioma cells through inhibition of IKB kinase/nuclear factor-KB pathway

Objective To investigate the effect of BMS-345541, a novel compound with a highly selective IκB kinase (IKK) inhibitory activity, on apoptosis of glioma cells and the possible mechanisms.Methods Human glioma cells U87MG were treated with different concentrations of BMS-345541. Cell apoptosis was investigated by Annexin V/PI staining assay. B cell lymphoma gene-2 (bcl-2) and Caspase-3 was detected by Western blotting. Nuclear factor-κB (NF-κB) activity was analyzed by NF-κB luciferase reporter gene assay and nuclear translocation of NF-κB was analyzed by Western blotting. Results After incubation with 1,10 and 20 μmol/L BMS-345541 ,apoptosis rates of U87MG cells were (18. 2 ±2. 2)% ,(49. 3 ± 3.6 ) % and ( 73.3 ± 8.9 ) %, respectively ( compared with the control, P ＜ 0. 01 ). BMS-345541 induced the activation of Caspase-3 and decreased expression of bcl-2. Moreover, NF-κB activity was decreased by( 66. 2 ± 5.1 )% ( P ＜ 0. 01 ) and nuclear translocation of NF-κB p65 subunit was inhibited.Conclusion BMS-345541 induced apoptosis of glioma cells involving inhibition of IKK/NF-κB signaling pathway. Key words: BMS-345541; Glioma; IKK; NF-κB; Apoptosis