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

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

  • Biochem Biophys Res Commun. 2014 Aug 15;451(1):112-8. doi: 10.1016/j.bbrc.2014.07.077.
Yun-Rong Zhu 1 Yong Xu 2 Jian-Feng Fang 1 Feng Zhou 1 Xiong-Wei Deng 1 Yun-Qing Zhang 3
Affiliations

Affiliations

  • 1 Department of Orthopedics, The Affiliated Jiangyin Hospital of Medical College of Southeast University, Jiangyin City, Jiangsu 214400, China.
  • 2 Department of Orthopedics, The Second Affiliated Hospital of Soochow University, Suzhou 215000, China.
  • 3 Department of Orthopedics, The Affiliated Jiangyin Hospital of Medical College of Southeast University, Jiangyin City, Jiangsu 214400, China. Electronic address: yunqingzhang@126.com.
Abstract

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.

Keywords

Apoptosis and signaling; Bufotalin; ER stress; Osteoblastoma.

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