Itraconazole suppresses the growth of glioblastoma through induction of autophagy: Involvement of abnormal cholesterol trafficking
Open accessAbstract
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.
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Itraconazole causes autophagic cell growth arrest in C6 and U87 glioblastoma cells in vitro and in a mouse U87 xenograft model.
“ITZ was discovered to cause autophagic cell growth arrest in C6 and U87 glioblastoma cells in a mouse xenograft (U87) model as well as in vitro.21”
From Itraconazole as a repurposed anti-cancer agent: focusing on synthesis, mechanisms of action and therapeutic insights (2026) · cites this paper as [21]
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- Authors
- Liu, R., Li, J., Zhang, T., Zou, L., Chen, Y., Wang, K., Lei, Y., Yuan, K., Li, Y., Lan, J., Cheng, L., Xie, N., Xiang, R., Nice, E. C., Huang, C., & Wei, Y.
- Affiliations
- Sichuan University (CN)
- Chengdu Medical College (CN)
- Chongqing Medical University (CN)
- Nankai University (CN)
- Monash University (AU)
- Corresponding author
- Huang, Canhua
- ORCID
- Venue
- Autophagy
- Publisher
- Informa UK Limited
- Published
- 2014-05-15
- Volume
- 10
- Issue
- 7
- Pages
- 1241-1255
- ISSN
- 1554-8627 (ISSN-L)
- 1554-8635
- PMC
- PMC4203550
- OpenAlex
- W2036586511
- Cited by
- 178
- References
- 77
- Citations by year
- 2026: 7 · 2025: 9 · 2024: 9 · 2023: 16 · 2022: 22 · 2021: 21 · 2020: 21 · 2019: 17 · 2018: 20 · 2017: 18 · 2016: 14 · 2015: 3 · 2014: 1
- FWCI
- 9.07
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Autophagy (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Natural Science Foundation of China (81172173, 2011CB910703, 2012ZX09501001-003, 81302205, J1103518, 2013CB911300)
- Ministry of Education, India
- National Science and Technology Major Project (2012ZX09501001-003, 2012ZX09501001)
- Topics
- Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
- Health Sciences › Medicine › Genetics › Glioma Diagnosis and Treatment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Lipids, and Metabolism
- Keywords
- itraconazole, glioblastoma, antifungal drug repurposing, cell proliferation inhibition, cholesterol transport, late endosomes, lysosomes, sterol carrier protein 2, anticancer activity
- MeSH terms
- Animals, Autophagy, Biological Transport, Brain Neoplasms, Carrier Proteins, Cell Membrane, Cholesterol, Female, Glioblastoma, Humans, Mice, Nude, Vacuoles, Signal Transduction, Itraconazole, Cell Line, Tumor, Cell Proliferation, Proto-Oncogene Proteins c-akt, Rats, TOR Serine-Threonine Kinases
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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