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

H Zhou, T Shen, C Shang, Y Luo, L Liu, J Yan, Y Li… - Oncotarget, 2014 - ncbi.nlm.nih.gov
H Zhou, T Shen, C Shang, Y Luo, L Liu, J Yan, Y Li, S Huang
Oncotarget, 2014ncbi.nlm.nih.gov
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 …
Abstract
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.
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