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Bufotalin-induced apoptosis in osteoblastoma cells is associated with endoplasmic reticulum stress activation

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机构: [a]Department of Orthopedics, The Affiliated Jiangyin Hospital of Medical College of Southeast University, Jiangyin City, Jiangsu 214400, China [b]Department of Orthopedics, The Second Affiliated Hospital of Soochow University, Suzhou 215000, China
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关键词: Osteoblastoma Bufotalin ER stress Apoptosis and signaling

摘要:
The search for novel and more efficient chemo-agents against malignant osteoblastoma is important. In this study, we examined the potential anti-osteoblastoma function of bufotalin, and studied the underlying mechanisms. Our results showed that bufotalin induced osteoblastoma cell death and apoptosis in dose- and time-dependent manners. Further, bufotalin induced endoplasmic reticulum (ER) stress activation in osteoblastoma cells, the latter was detected by the induction of C/EBP homologous protein (CHOP), phosphorylation of inositol-requiring enzyme 1 (IRE1) and PKR-like endoplasmic reticulum kinase (PERK), as well as caspase-12 activation. Conversely, the ER stress inhibitor salubrinal, the caspase-12 inhibitor z-ATAD-fmk as well as CHOP depletion by shRNA significantly inhibited bufotalin-induced osteoblastoma cell death and apoptosis. Finally, by using a mice xenograft model, we demonstrated that bufotalin inhibited U2OS osteoblastoma cell growth in vivo. In summary, our results suggest that ER stress contributes to bufotalin-induced apoptosis in osteoblastoma cells. Bufotalin might be investigated as a novel anti-osteoblastoma agent. (C) 2014 Elsevier Inc. All rights reserved.

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出版当年[2013]版:
大类 | 3 区 生物
小类 | 4 区 生化与分子生物学 4 区 生物物理
最新[2023]版:
大类 | 3 区 生物学
小类 | 3 区 生物物理 4 区 生化与分子生物学
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出版当年[2012]版:
Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY Q3 BIOPHYSICS
最新[2023]版:
Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY Q3 BIOPHYSICS

影响因子: 最新[2023版] 最新五年平均 出版当年[2012版] 出版当年五年平均 出版前一年[2011版] 出版后一年[2013版]

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第一作者机构: [a]Department of Orthopedics, The Affiliated Jiangyin Hospital of Medical College of Southeast University, Jiangyin City, Jiangsu 214400, China
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通讯机构: [*]Department of Orthopedics, The Affiliated Jiangyin Hospital of Medical College of Southeast University, No. 163 Shoushan Rd, Jiangyin City, Jiangsu 215600, China
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