期刊
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
卷 515, 期 1, 页码 9-15出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bbrc.2019.05.070
关键词
Tigecycline; Mitochondrial translation; Osteosarcoma; EF-Tu
资金
- Yangtze University [201601616]
The unique dependence of cancer cells on mitochondrial metabolism has been exploited therapeutically in various cancers but not osteosarcoma. In this work, we demonstrate that inhibition of mitochondria! translation is effective and selective in targeting osteosarcoma. We firstly showed that tigecycline at pharmacological achievable concentrations inhibited growth and induced apoptosis of multiple osteosarcoma cell lines while sparing normal osteoblast cells. Similarly, tigecycline at effective doses that delayed osteosarcoma growth did not cause significant toxicity to mice. We next showed that tigecycline specifically inhibits mitochondrial translation, resulting in defective mitochondrial respiration in both osteosarcoma and normal osteoblast cells. We further confirm mitochondrial respiration as the target of tigecycline using three independent approaches. In addition, we demonstrate that compared to normal osteoblasts, osteosarcoma cells have higher mitochondrial biogenesis. We finally show that specific inhibition of mitochondrial translation via EF-Tu depletion produces the similar anti-osteosarcoma effects of tigecycline. Our work highlights the therapeutic value of targeting mitochondrial metabolism in osteosarcoma and tigecycline as a useful addition to the treatment of osteosarcoma. (C) 2019 Elsevier Inc. All rights reserved.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据