title: Brucine induces the apoptosis of U266 multiple myeloma cells by phosphorylation             of c-Jun.
abstract: The aim of this study was to investigate the mechanism of the apoptotic effect of brucine on human multiple myeloma (MM) cells. U266 cells (5x104) were plated in the presence or absence of brucine (0, 0.05, 0.1, 0.2 and 0.4 mg/ml) in 96‑well culture plates for 24‑72 h. The anti-proliferative response to brucine was assessed by MTT assay. Analysis of the cell cycle of U266 cells treated with or without brucine was performed using flow cytometry. The expression change of c-Jun following treatment with brucine or brucine plus the c-Jun N-terminal kinase (JNK)-specific inhibitor SP600125 was detected using RT-PCR. Brucine appeared to have an effect on apoptosis in a dose- and time‑dependent manner. Cell cycle analysis using flow cytometry revealed the accumulation of cells at the sub-G0/G1 phase. The apoptotic rates were 4.137, 10.55, 12.31, 27.67 and 29.67% (0, 0.05, 0.1, 0.2, 0.4 mg/ml brucine, respectively; P<0.01). The gray scale values were 0.7961 ± 0.007 and 0.4683 ± 0.003 (mRNA expression of c-Jun of U266 cells with or without SP600125, respectively). Concentrations of ≤ 0.4 mg/ml brucine induced apoptosis in U266 cells. Thus, brucine‑induced apoptosis in U266 cells occurs via the JNK signaling pathway and phosphorylation of c-Jun.
authors.affiliation: Department of Hematology, The Second Hospital of Shanxi Medical University, Taiyuan, Shanxi 030001, P.R. China. mayanpingcn@126.com
authors.forename: Yanping
authors.initials: Y
authors.lastname: Ma
authors.forename: Zhihua
authors.initials: Z
authors.lastname: Li
authors.forename: Yihua
authors.initials: Y
authors.lastname: Wang
authors.forename: Jing
authors.initials: J
authors.lastname: Feng
mesh_terms: D000276:Adjuvants, Immunologic / Q000633:toxicity*; D000873:Anthracenes / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000378:metabolism; D045744:Cell Line, Tumor; D059585:G1 Phase Cell Cycle Checkpoints / Q000187:drug effects; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D009101:Multiple Myeloma / Q000378:metabolism / Q000473:pathology; D010766:Phosphorylation; D015398:Signal Transduction / Q000187:drug effects; D013331:Strychnine / Q000031:analogs & derivatives* / Q000633:toxicity
chemical_list: D000276:Adjuvants, Immunologic; D000873:Anthracenes; C432165:pyrazolanthrone; C083806:brucine; D048031:JNK Mitogen-Activated Protein Kinases; D053148:Caspase 3; D013331:Strychnine