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.

• Authors: Ying Xu, Qian Wang, Xiaozhen Li, Yingyan Chen, Gang Xu
• Journal: Environmental toxicology (Environ Toxicol) Vol. 36 Issue 2 Pg. 257-266 (Feb 2021) ISSN: 1522-7278 [Electronic] United States
• PMID: 32951314 (Publication Type: Journal Article)
• Copyright: © 2020 Wiley Periodicals LLC.

Chemical References

• Itraconazole

Topics

• Animals
• Cell Line, Tumor
• Cell Survival (drug effects)
• Female
• Ferroptosis (drug effects)
• Humans
• Itraconazole (pharmacology)
• Mice, Nude
• Nasopharyngeal Carcinoma (drug therapy, pathology)
• Nasopharyngeal Neoplasms (drug therapy, pathology)
• Neoplastic Stem Cells (drug effects, pathology)
• Radiation Tolerance (drug effects)
• Spheroids, Cellular (drug effects, pathology)
• Xenograft Model Antitumor Assays
• Mice