Abstract 3408: The anticancer mechanisms of ciclopirox olamine.

Ciclopirox olamine (CPX), a synthetic fungicide clinically used to treat mycoses of the skin and nails, has been demonstrated as a novel anticancer agent. However, the underlying anticancer mechanisms are not well understood. Here we show that CPX suppressed cell proliferation, induced cell death (apoptosis and autophagy), and inhibited cell motility in breast cancer (MDA-MB-231) and rhabdomyosarcoma (Rh30) cells. We observed that CPX induced inhibitory phosphorylation of CDK2 and inhibited cyclin D1 expression, resulting in dephosphorylation of Rb in the tumor cells, which was correlated to cell cycle arrest at G1 phase. Furthermore, we found that CPX caused DNA damage and activated ATR-Chk1 axis, increasing phosphorylation and degradation of Cdc25A, a critical protein involved in the regulation of cell cycle progression and apoptosis. CPX also activated JNK cascade, associated with apoptosis. Moreover, CPX downregulated cellular protein expression of small GTPases (RhoA, Cdc42 and Rac1) and induced inhibitory phosphorylation of FAK, related to cell migration. In addition, we found that CPX inhibited the signaling of mTOR, a central controller of cell proliferation, survival (apoptosis and autophagy) and motility. The results suggest that CPX exerts its anticancer activity by targeting multiple signaling molecules. Citation Format: Tao Shen, Hongyu Zhou, Shile Huang. The anticancer mechanisms of ciclopirox olamine. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3408. doi:10.1158/1538-7445.AM2013-3408