4.7 Article

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

Journal

EUROPEAN JOURNAL OF PHARMACOLOGY
Volume 844, Issue -, Pages 204-215

Publisher

ELSEVIER SCIENCE BV
DOI: 10.1016/j.ejphar.2018.12.019

Keywords

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

Funding

  1. National Natural Science Foundation of China [81803552, 81573453, 81603126]
  2. China Postdoctoral Science Foundation [2017M621958]
  3. Fundamental Research Funds for the Central Universities

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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 NAG 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.

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