Hiroshi Tsubamoto1,2, Kayo Inoue3, Kazuko Sakata3, Tomoko Ueda3, Ryu Takeyama3, Hiroaki Shibahara3, Takashi Sonoda2. 1. Department of Obstetrics and Gynecology, Hyogo College of Medicine, Nishinomiya, Japan tsuba@hyo-med.ac.jp. 2. Department of Medical Oncology, Meiwa Hospital, Nishinomiya, Japan. 3. Department of Obstetrics and Gynecology, Hyogo College of Medicine, Nishinomiya, Japan.
Abstract
BACKGROUND: Itraconazole is a common antifungal agent that has demonstrated anticancer activity in preclinical and clinical studies. This study investigated whether itraconazole exerts this effect in endometrial cancer (EC) cells. MATERIALS AND METHODS: Cell viability was evaluated with the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, and gene and protein expression were assessed by microarray analysis and immunoblotting, respectively, in five EC cell lines. RESULTS: Itraconazole-suppressed proliferation of AN3-CA, HEC-1A and Ishikawa cells (p<0.05) but not of HEC-50B or SNG-II cells. Itraconazole did not suppress GLI1 or GLI2 transcription but did inhibit the expression of mammalian target of rapamycin (mTOR) signaling components in AN3-CA and HEC-1A cells, while inducing that of microtubule-associated protein 1A/1B-light chain 3-II, a marker of autophagy. ATP-binding cassette transporter A1 gene was down-regulated in Ishikawa, HEC-50B and SNG-II cells. CONCLUSION: Itraconazole treatment suppresses the growth of EC cells by inhibiting AKT/mTOR signalling. Copyright
BACKGROUND:Itraconazole is a common antifungal agent that has demonstrated anticancer activity in preclinical and clinical studies. This study investigated whether itraconazole exerts this effect in endometrial cancer (EC) cells. MATERIALS AND METHODS: Cell viability was evaluated with the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, and gene and protein expression were assessed by microarray analysis and immunoblotting, respectively, in five EC cell lines. RESULTS:Itraconazole-suppressed proliferation of AN3-CA, HEC-1A and Ishikawa cells (p<0.05) but not of HEC-50B or SNG-II cells. Itraconazole did not suppress GLI1 or GLI2 transcription but did inhibit the expression of mammalian target of rapamycin (mTOR) signaling components in AN3-CA and HEC-1A cells, while inducing that of microtubule-associated protein 1A/1B-light chain 3-II, a marker of autophagy. ATP-binding cassette transporter A1 gene was down-regulated in Ishikawa, HEC-50B and SNG-II cells. CONCLUSION:Itraconazole treatment suppresses the growth of EC cells by inhibiting AKT/mTOR signalling. Copyright
Authors: George Mihai Nitulescu; Maryna Van De Venter; Georgiana Nitulescu; Anca Ungurianu; Petras Juzenas; Qian Peng; Octavian Tudorel Olaru; Daniela Grădinaru; Aristides Tsatsakis; Dimitris Tsoukalas; Demetrios A Spandidos; Denisa Margina Journal: Int J Oncol Date: 2018-10-16 Impact factor: 5.650