BackgroundGlobally, lung cancer is one of the most malignant tumors, of which lung adenocarcinoma (LUAD) is the most common subtype, with a particularly poor prognosis. Ciclopirox olamine (CPX) is an antifungal drug and was recently identified as a potential antitumor agent. However, how CPX and its mechanism of action function during LUAD remain unclear.MethodsThe effects of CPX on cell proliferation, cell cycle, reactive oxygen species (ROS) levels, and apoptosis were assessed using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay, colony formation, western blotting, flow cytometry assays, and immunohistochemistry. Global gene expression levels were compared between control and CPX-treated LUAD cells. A LUAD xenograft mouse model was used to evaluate the potential in vivo effects of CPX.ResultsWe observed that CPX displayed strong antitumorigenic properties in LUAD cells, inhibited LUAD proliferation, induced ROS production, caused DNA damage, and activated the ATR-CHK1-P53 pathway. Topoisomerase II alpha (TOP2A) is overexpressed in LUAD and associated with a poor prognosis. By analyzing differentially expressed genes (DEGs), TOP2A was significantly down-regulated in CPX-treated LUAD cells. Furthermore, CPX treatment substantially inhibited in vivo LUAD xenograft growth without toxicity or side effects to the hematological system and internal organs.ConclusionsCollectively, for the first time, we showed that CPX exerted tumor-suppressor effects in LUAD via TOP2A, suggesting CPX could potentially function as a promising chemotherapeutic for LUAD treatment.
