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Itraconazole suppresses the growth of glioblastoma through induction of autophagy: Involvement of abnormal cholesterol trafficking.

Al's Comment:

 Itraconazole is an antifungal drug used to treat fungal toenails and other fungal infections.  It is very safe with minimal side effects.  It has been tested for use in other cancers. A recent study http://med.stanford.edu/news/all-news/2014/02/oral-anti-fungal-drug-can-treat-skin-cancer-in-patients-study-shows.html showed that it can reduce the size of skin cancers.  

  


Posted on: 06/19/2014

Autophagy. 2014 May 15;10(7). [Epub ahead of print]
Itraconazole suppresses the growth of glioblastoma through induction of autophagy: Involvement of abnormal cholesterol trafficking.
Liu R1, Li J2, Zhang T2, Zou L3, Chen Y4, Wang K5, Lei Y6, Yuan K5, Li Y5, Lan J5, Cheng L5, Xie N5, Xiang R7, Nice EC8, Huang C5, Wei Y5.
Author information: 
1State Key Laboratory of Biotherapy; West China Hospital; Sichuan University; Chengdu, China; State Key Laboratory of Oral Diseases; West China Hospital of Stomatology; Sichuan University; Chengdu, China.
2School of Biomedical Sciences; Chengdu Medical College; Chengdu, China.
3College of Life Sciences; Sichuan University; Chengdu, China.
4Department of Gastrointestinal Surgery; State Key Laboratory of Biotherapy; West China Hospital, Sichuan University, Chengdu, China.
5State Key Laboratory of Biotherapy; West China Hospital; Sichuan University; Chengdu, China.
6Department of Biochemistry and Molecular Biology, Molecular Medicine and Cancer Research Center; Chongqing Medical University; Chongqing, China.
7School of Medicine; Nankai University; Tianjin, China.
8Department of Biochemistry and Molecular Biology; Monash University; Clayton, Victoria Australia.
 
Abstract
Glioblastoma is one of the most aggressive human cancers with poor prognosis, and therefore a critical need exists for novel therapeutic strategies for management of glioblastoma patients. Itraconazole, a traditional antifungal drug, has been identified as a novel potential anticancer agent due to its inhibitory effects on cell proliferation and tumor angiogenesis; however, the molecular mechanisms involved are still unclear. Here, we show that itraconazole inhibits the proliferation of glioblastoma cells both in vitro and in vivo. Notably, we demonstrate that treatment with itraconazole induces autophagic progression in glioblastoma cells, while blockage of autophagy markedly reverses the antiproliferative activities of itraconazole, suggesting an antitumor effect of autophagy in response to itraconazole treatment. Functional studies revealed that itraconazole retarded the trafficking of cholesterol from late endosomes and lysosomes to the plasma membrane by reducing the levels of SCP2, resulting in repression of AKT1-MTOR signaling, induction of autophagy, and finally inhibition of cell proliferation. Together, our studies provide new insights into the molecular mechanisms regarding the antitumor activities of itraconazole, and may further assist both the pharmacological investigation and rational use of itraconazole in potential clinical applications.
 
 PMID: 24905460 [PubMed - as supplied by publisher] 
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