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Miconazole induces autophagic death in glioblastoma cells via reactive oxygen species-mediated endoplasmic reticulum stress

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Author(s)
Hui-Jung JungIncheol SeoBijay Kumar JhaSeong-Il SuhWon-Ki Baek
Keimyung Author(s)
Suh, Seong IlBaek, Won Ki
Department
Dept. of Microbiology (미생물학)
Journal Title
Oncol Lett
Issued Date
2021
Volume
21
Issue
4
Abstract
Miconazole is an antifungal agent that is used for the treatment of superficial mycosis. However, recent studies have indicated that miconazole also exhibits potent anticancer effects in various types of cancer via the activation of apoptosis. The main aim of the present study was to observe the effect of miconazole on autophagic cell death of cancer cells. Cytotoxicity was measured by viable cell counting after miconazole treatment in glioblastoma cell lines (U343MG, U87MG and U251MG). Induction of autophagy was analyzed by examining microtubule‑associated protein light chain 3 (LC3)‑II expression levels using western blotting and by detecting GFP‑LC3 translocation using a fluorescence microscope. Intracellular ROS production was measured using a fluorescent probe, 2',7'‑dichlorodihydrofluorescein diacetate. It was found that miconazole induced autophagic cell death in the U251MG glioblastoma cell line via the generation of reactive oxygen species (ROS) and endoplasmic reticulum (ER) stress response. An association between miconazole‑induced ROS production and autophagy was also identified; in particular, pretreatment of the cells with a ROS scavenger resulted in a reduction in the levels of LC3‑II. Miconazole‑induced ER stress was associated with increases in binding immunoglobulin protein (BiP), inositol‑requiring enzyme 1α (IRE1α) and CHOP expression, and phospho‑eIF2α levels. The inhibition of ER stress via treatment with 4‑phenylbutyric acid or BiP knockdown reduced miconazole‑induced autophagy and cell death. These findings suggest that miconazole induces autophagic cell death by inducing an ROS‑dependent ER stress response in U251MG glioma cancer cells and provide new insights into the potential antiproliferative effects of miconazole.
Keimyung Author(s)(Kor)
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Publisher
School of Medicine (의과대학)
Citation
Hui-Jung Jung et al. (2021). Miconazole induces autophagic death in glioblastoma cells via reactive oxygen species-mediated endoplasmic reticulum stress. Oncol Lett, 21(4), 335. doi: 10.3892/ol.2021.12596
Type
Article
ISSN
1792-1082
Source
https://www.spandidos-publications.com/10.3892/ol.2021.12596
DOI
10.3892/ol.2021.12596
URI
https://kumel.medlib.dsmc.or.kr/handle/2015.oak/43645
Appears in Collections:
1. School of Medicine (의과대학) > Dept. of Microbiology (미생물학)
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