Itraconazole attenuates the stemness of nasopharyngeal carcinoma cells via triggering ferroptosis
Abstract
Radiotherapy is a common therapy method for nasopharyngeal carcinoma (NPC) treatment; however, radioresistance greatly limits the clinical efficiency and prognosis of NPC patients. Therefore, it is extremely urgent to reveal the underlying mechanism contributing to radioresistance and find possible diagnostic biomarkers. Here, we collected the spheroids formed by NPC cells, which had been confirmed to hold the stem cell‐like traits, and found that these spheroids exhibited a certain degree of radioresistance. Additionally, NPC spheroids displayed a certain degree of ferroptosis resistance, as evident by the decrease of iron concentration in lysosomes and lipid peroxides oxygen, and increase of glutathione (GSH) level. Furthermore, we revealed that itraconazole triggered the ferroptosis of NPC spheroids, which is characterized as the increase of iron concentration and lipid peroxides oxygen, and decrease of GSH level, and decreased the cell viability of NPC spheroids. Notably, itraconazole partially reversed the radioresistance of NPC spheroids. Mechanistically, we found that itraconazole can sequester iron in lysosome and thus trigger ferroptosis; this is essential for itraconazole‐mediated attenuation on NPC spheroid stemness. Therefore, this study provides evidences showing that itraconazole might be used for killing NPC stem cells and thus attenuate radioresistance.
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NPC spheroids showed some degree of radioresistance and resistance to ferroptosis.
“Xu, Ying, et al.88 collected the spheroids produced by NPC cells—which were shown to possess stem cell-like characteristics—they discovered that these spheroids showed some degree of radioresistance. Additionally, NPC spheroids showed some resistance to ferroptosis, as evidenced by an increase in glutathione (GSH) and a decrease in iron concentration in lipid peroxides and lysosomes.”
From Itraconazole as a repurposed anti-cancer agent: focusing on synthesis, mechanisms of action and therapeutic insights (2026) · cites this paper as [88]
ITZ can cause ferroptosis by sequestering iron in the lysosome, and this is necessary for ITZ-mediated attenuation of NPC spheroid stemness.
“In terms of mechanism, this study discovered that ITZ can cause ferroptosis by sequestering iron in the lysosome; this is necessary for ITZ-mediated attenuation of NPC spheroid stemness.”
From Itraconazole as a repurposed anti-cancer agent: focusing on synthesis, mechanisms of action and therapeutic insights (2026) · cites this paper as [88]
ITZ caused ferroptosis in NPC spheroids, defined as an increase in iron concentration and lipid peroxide oxygen, a drop in GSH levels, and a reduction in NPC spheroid cell viability.
“ITZ also caused ferroptosis in NPC spheroids, which is defined as an increase in iron concentration and lipid peroxide oxygen, a drop in GSH levels, and a reduction in NPC spheroids' cell viability.”
From Itraconazole as a repurposed anti-cancer agent: focusing on synthesis, mechanisms of action and therapeutic insights (2026) · cites this paper as [88]
It is possible to utilize ITZ to kill NPC stem cells and thereby reduce radioresistance.
“Consequently, this work offers proof that it is possible to utilize ITZ to kill NPC stem cells and thereby reduce radioresistance.”
From Itraconazole as a repurposed anti-cancer agent: focusing on synthesis, mechanisms of action and therapeutic insights (2026) · cites this paper as [88]
ITZ partially reversed the radioresistance of NPC spheroids.
“Notably, NPC spheroids' radioresistance was partially reversed by ITZ.”
From Itraconazole as a repurposed anti-cancer agent: focusing on synthesis, mechanisms of action and therapeutic insights (2026) · cites this paper as [88]
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- Authors
- Xu, Y., Wang, Q., Li, X., Chen, Y., & Xu, G.
- Affiliations
- Second Affiliated Hospital of Xi'an Jiaotong University (CN)
- Corresponding author
- Xu, Gang
- Venue
- Environmental Toxicology
- Publisher
- Wiley
- Published
- 2020-09-20
- Volume
- 36
- Issue
- 2
- Pages
- 257-266
- ISSN
- 1520-4081 (ISSN-L)
- 1522-7278
- OpenAlex
- W3087461016
- Cited by
- 51
- References
- 35
- Citations by year
- 2026: 3 · 2025: 11 · 2024: 11 · 2023: 12 · 2022: 9 · 2021: 4 · 2020: 1
- FWCI
- 3.66
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Environmental Toxicology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Ferroptosis and cancer prognosis
- Health Sciences › Medicine › Otorhinolaryngology › Head and Neck Cancer Studies
- Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
- Keywords
- itraconazole, nasopharyngeal carcinoma, ferroptosis, radioresistance (biology), cancer stem cells, tumor spheroids, glutathione, lipid peroxidation, radiosensitization
- MeSH terms
- Nasopharyngeal Carcinoma, Ferroptosis, Animals, Cell Survival, Female, Humans, Mice, Nude, Nasopharyngeal Neoplasms, Radiation Tolerance, Neoplastic Stem Cells, Itraconazole, Spheroids, Cellular, Xenograft Model Antitumor Assays, Cell Line, Tumor, Mice
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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