1. Academic Validation
  2. 2-Bromopalmitate sensitizes osteosarcoma cells to adriamycin-induced apoptosis via the modulation of CHOP

2-Bromopalmitate sensitizes osteosarcoma cells to adriamycin-induced apoptosis via the modulation of CHOP

  • Eur J Pharmacol. 2019 Feb 5;844:204-215. doi: 10.1016/j.ejphar.2018.12.019.
Tong Xu 1 Chao Huang 1 Xiao-Tian Qi 1 Xiao-Chun Yang 1 Ning Zhang 2 Ji Cao 1 Chen Wang 1 Hong Zhu 1 Bo Yang 1 Qiao-Jun He 1 Xue-Jing Shao 3 Mei-Dan Ying 4
Affiliations

Affiliations

  • 1 Institute of Pharmacology and Toxicology, Zhejiang Province Key Laboratory of Anti-Cancer Drug Research, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China.
  • 2 Department of Orthopedics, The Second Affiliated Hospital of Zhejiang University, Zhejiang University, Hangzhou 310009, China.
  • 3 Institute of Pharmacology and Toxicology, Zhejiang Province Key Laboratory of Anti-Cancer Drug Research, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China. Electronic address: xjshao@zju.edu.cn.
  • 4 Institute of Pharmacology and Toxicology, Zhejiang Province Key Laboratory of Anti-Cancer Drug Research, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China. Electronic address: mying@zju.edu.cn.
Abstract

Osteosarcoma is the most common primary malignant bone tumour, but the survival rate of patients has plateaued since the mid-1980s. Adriamycin is an integral component of the current first-line chemotherapies used for osteosarcoma, but dose-dependent severe side effects often limit its clinical application. Here, we propose a potential combination regimen in which adriamycin plus 2-bromopalmitate, a palmitoylation inhibitor, exhibited powerful therapeutic effects on osteosarcoma. First, 2-bromopalmitate strongly increased the proliferation inhibition of adriamycin in both human osteosarcoma cell lines and primary osteosarcoma cells. Adriamycin-induced Apoptosis in osteosarcoma cells was enhanced when synergized with 2-bromopalmitate. Our study indicated that the Reactive Oxygen Species scavenger NAC and GSH could largely reverse the Apoptosis induced by adriamycin combined with 2-bromopalmitate, demonstrating that Reactive Oxygen Species played an essential role in this combination therapy. Moreover, CHOP was remarkably elevated in the combination group, and silencing of CHOP almost completely blocked the Apoptosis induced by the combination of 2-bromopalmitate and adriamycin. Taken together, our study provides a prospective therapeutic strategy to eliminate osteosarcoma, which is propitious to clinical combination therapy development.

Keywords

2-Bromopalmitate; Adriamycin; CHOP; Osteosarcoma; Reactive oxygen species.

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