Ciclopirox induces autophagy through reactive oxygen species-mediated activation of JNK signaling pathway

• DOI: 10.18632/oncotarget.2471
• Publication Date: 2015-09-15T23:37:39Z
• Authors: Hongyu Zhou; Tao Shen; Chaowei Shang; Yan Luo; Lei Liu; Juming Yan; Yan Li; Shile Huang
• Keywords: 0301 basic medicine; Antifungal Agents; MAP Kinase Signaling System; Pyridones; JNK Mitogen-Activated Protein Kinases; Antineoplastic Agents; Ciclopirox; 3. Good health; 03 medical and health sciences; Cell Line, Tumor; Rhabdomyosarcoma; Autophagy; Humans; Reactive Oxygen Species

Ciclopirox olamine (CPX), a fungicide, has been demonstrated as potential anticancer agent. However, the underlying mechanism is not well understood. Here, we found that CPX induced autophagy in human rhabdomyosarcoma (Rh30 and RD) cells. It appeared CPX-induced was attributed to induction of reactive oxygen species (ROS), N-acetyl-L-cysteine (NAC), ROS scavenger antioxidant, prevented this process. Furthermore, observed activation mitogen-activated protein kinases (MAPKs), including extracellular signal-regulated kinase 1/2 (ERK1/2), c-Jun N-terminal (JNK) p38 MAPK, which also blocked by NAC. only inhibition JNK (with SP600125) or expression dominant negative partially autophagy, indicating ROS-mediated signaling pathway contributed autophagy. Of interest, chloroquine (CQ) enhanced cell death, plays pro-survival role Our finding suggests combination with inhibitors may be novel strategy potentiating activity for treatment rhabdomyosarcoma.