Reference - Detail
|Author||Ueda T, Tsubamoto H, Inoue K, Sakata K, Shibahara H, Sonoda T.|
|Title||Itraconazole Modulates Hedgehog, WNT/β-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 β-catenin expression and Akt phosphorylation.
CONCLUSION:Itraconazole is a multi-targeting anticancer agent and a promising therapeutic agent for cervical cancer.
|MeSH||ATP-Binding Cassette Transporters / metabolism Antineoplastic Agents / pharmacology Carrier Proteins / metabolism Cell Line, Tumor Cell Proliferation / drug effects* Down-Regulation / drug effects Female HeLa Cells Hedgehog Proteins / metabolism* Humans Itraconazole / pharmacology* Proto-Oncogene Proteins c-akt / metabolism* Signal Transduction / drug effects Uterine Cervical Neoplasms / drug therapy* Uterine Cervical Neoplasms / metabolism Wnt Proteins / metabolism* Wnt4 Protein / metabolism Zinc Finger Protein GLI1 / metabolism beta Catenin / metabolism*|
|Human and Animal Cells||HeLa(RCB0007) Ca Ski(RCB1947)|