Itraconazole Modulates Hedgehog, Wnt/Beta-Catenin, As Well As Akt Signalling, And Inhibits Proliferation Of Cervical Cancer Cells

Background/Aim: Repurposing itraconazole as an anticancer agent has been evaluated in several studies. The present study investigated whether itraconazole exerts an anticancer effect on cervical cancer cells. Materials and Methods: CaSki and HeLa cells were cultured in itraconazole and vehicle after which colony-forming and cell viability assays were performed. Transcription and protein expression were assessed by cDNA microarray analysis and immunoblotting, respectively. Results: Itraconazole suppressed proliferation of CaSki and HeLa cells in a dose- and time-dependent manner. Furthermore, CaSki cells were more significantly affected by itraconazole than HeLa cells. The microarray analysis showed an 8-fold down-regulation in the expression of GLI1, WNT4 and WNT10A among itraconazole-treated CaSki cells. Moreover, the transcription of sterol carrier protein-2 and ATP-binding cassette transporter-1 was unaffected by itraconazole. Immunoblots showed suppression in beta-catenin expression and Akt phosphorylation. Conclusion: Itraconazole is a multi-targeting anticancer agent and a promising therapeutic agent for cervical cancer.