Ciclopirox induces autophagy through reactive oxygen species-mediated activation of JNK signaling pathway
Zhou, Hongyu1,2; Shen, Tao2; Shang, Chaowei2; Luo, Yan2; Liu, Lei2; Yan, Juming1; Li, Yan1; Huang, Shile2,3
2014-10-30
发表期刊ONCOTARGET
卷号5期号:20页码:10140-10150
摘要Ciclopirox olamine (CPX), a fungicide, has been demonstrated as a potential anticancer agent. However, the underlying anticancer mechanism is not well understood. Here, we found that CPX induced autophagy in human rhabdomyosarcoma (Rh30 and RD) cells. It appeared that CPX-induced autophagy was attributed to induction of reactive oxygen species (ROS), as N-acetyl-L-cysteine (NAC), a ROS scavenger and antioxidant, prevented this process. Furthermore, we observed that CPX induced activation of mitogen-activated protein kinases (MAPKs), including extracellular signal-regulated kinase 1/2 (ERK1/2), c-Jun N-terminal kinase (JNK) and p38 MAPK, which was also blocked by NAC. However, only inhibition of JNK (with SP600125) or expression of dominant negative c-Jun partially prevented CPX-induced autophagy, indicating that ROS-mediated activation of JNK signaling pathway contributed to CPX-induced autophagy. Of interest, inhibition of autophagy by chloroquine (CQ) enhanced CPX-induced cell death, indicating that CPX-induced autophagy plays a pro-survival role in human rhabdomyosarcoma cells. Our finding suggests that the combination with autophagy inhibitors may be a novel strategy in potentiating the anticancer activity of CPX for treatment of rhabdomyosarcoma.
关键词Ciclopirox Autophagy Rhabdomyosarcoma Reactive Oxygen Species Jnk
收录类别SCI
语种英语
WOS研究方向Oncology ; Cell Biology
WOS类目Oncology ; Cell Biology
WOS记录号WOS:000348036500048
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文献类型期刊论文
条目标识符http://ir.kib.ac.cn/handle/151853/20414
专题植物化学与西部植物资源持续利用国家重点实验室
作者单位1.Chinese Acad Sci, Kunming Inst Bot, State Key Lab Phytochem & Plant Resources West Ch, Kunming 650201, Peoples R China
2.Louisiana State Univ, Hlth Sci Ctr, Dept Biochem & Mol Biol, Shreveport, LA 71130 USA
3.Louisiana State Univ, Hlth Sci Ctr, Feist Weiller Canc Ctr, Shreveport, LA 71130 USA
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Zhou, Hongyu,Shen, Tao,Shang, Chaowei,et al. Ciclopirox induces autophagy through reactive oxygen species-mediated activation of JNK signaling pathway[J]. ONCOTARGET,2014,5(20):10140-10150.
APA Zhou, Hongyu.,Shen, Tao.,Shang, Chaowei.,Luo, Yan.,Liu, Lei.,...&Huang, Shile.(2014).Ciclopirox induces autophagy through reactive oxygen species-mediated activation of JNK signaling pathway.ONCOTARGET,5(20),10140-10150.
MLA Zhou, Hongyu,et al."Ciclopirox induces autophagy through reactive oxygen species-mediated activation of JNK signaling pathway".ONCOTARGET 5.20(2014):10140-10150.
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