Abstract 2111: Ciclopirox inhibits tumor cell motility by suppressing protein expression of small GTPases and phosphorylation of paxillin

Abstract

Abstract Ciclopirox olamine (CPX), an off-patent antifungal drug, is used for the treatment of superficial mycoses. Recent studies have demonstrated that CPX also possesses potent anticancer activity by inhibiting cell proliferation and inducing cell death in tumor cells. However, it is unknown whether CPX inhibits cell motility. In the present study, we found that CPX potently inhibited cell motility in a concentration-dependent manner in rhabdomyosarcoma (Rh30 and RD) cells, which was independent of the reduction of cell viability. As small GTPases (RhoA, Cdc42, and Rac1) and focal adhesion proteins (paxillin) play critical roles in the regulation of cell motility, we further studied whether CPX affects these proteins. Our Western blot analysis revealed that CPX did inhibit cellular protein expression of RhoA, Cdc42 and Rac1. However, by RT-PCR analysis, CPX did not alter the mRNA levels of the small GTPases. As microRNAs (miRNAs) can regulate protein expression at transcriptional and post-transcriptional levels, we investigated the effect of CPX on the expression of miRNAs. Our miRNA PCR array revealed that treatment with 10 μM of CPX for 24 hours upregulated the expression of 27 miRNAs by 2.04-6.10 fold, and downregulated the expression of 7 miRNAs by 2.00-7.89 fold in Rh30 cells. Further research is ongoing to identify whether these up/downregulated miRNAs are linked to the reduced expression of small GTPases and potentially more proteins. In addition, we found that CPX inhibited the phosphorylation of paxillin, despite no effect on the total cellular protein expression. The results suggest that CPX inhibits tumor cell motility at least by suppressing the protein expression of small GTPases and the phosphorylation of paxillin. Supported by the Feist-Weiller Cancer Center, LSU Health Sciences Center, Shreveport, LA. Citation Format: Shile Huang, Tao Shen. Ciclopirox inhibits tumor cell motility by suppressing protein expression of small GTPases and phosphorylation of paxillin [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2111. doi:10.1158/1538-7445.AM2017-2111