Open Access

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

  • Authors:
    • Hui-Jung Jung
    • Incheol Seo
    • Bijay Kumar Jha
    • Seong-Il Suh
    • Won-Ki Baek
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  • Published online on: February 25, 2021     https://doi.org/10.3892/ol.2021.12596
  • Article Number: 335
  • Copyright: © Jung et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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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.
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April-2021
Volume 21 Issue 4

Print ISSN: 1792-1074
Online ISSN:1792-1082

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Spandidos Publications style
Jung H, Seo I, Jha BK, Suh S and Baek W: Miconazole induces autophagic death in glioblastoma cells via reactive oxygen species‑mediated endoplasmic reticulum stress. Oncol Lett 21: 335, 2021
APA
Jung, H., Seo, I., Jha, B.K., Suh, S., & Baek, W. (2021). Miconazole induces autophagic death in glioblastoma cells via reactive oxygen species‑mediated endoplasmic reticulum stress. Oncology Letters, 21, 335. https://doi.org/10.3892/ol.2021.12596
MLA
Jung, H., Seo, I., Jha, B. K., Suh, S., Baek, W."Miconazole induces autophagic death in glioblastoma cells via reactive oxygen species‑mediated endoplasmic reticulum stress". Oncology Letters 21.4 (2021): 335.
Chicago
Jung, H., Seo, I., Jha, B. K., Suh, S., Baek, W."Miconazole induces autophagic death in glioblastoma cells via reactive oxygen species‑mediated endoplasmic reticulum stress". Oncology Letters 21, no. 4 (2021): 335. https://doi.org/10.3892/ol.2021.12596