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Research ArticleExperimental Studies

Down-regulation of Glutathione Peroxidase 4 in Oral Cancer Inhibits Tumor Growth Through SREBP1 Signaling

MASAKATSU FUKUDA, YUDAI OGASAWARA, HIROYASU HAYASHI, AYAKO OKUYAMA, JUNYA SHIONO, KATSUYUKI INOUE and HIDEAKI SAKASHITA
Anticancer Research April 2021, 41 (4) 1785-1792; DOI: https://doi.org/10.21873/anticanres.14944
MASAKATSU FUKUDA
Division of Oral and Maxillofacial Surgery, Department of Diagnostic and Therapeutic Sciences, Meikai University School of Dentistry, Saitama, Japan
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  • For correspondence: fukudam@dent.meikai.ac.jp
YUDAI OGASAWARA
Division of Oral and Maxillofacial Surgery, Department of Diagnostic and Therapeutic Sciences, Meikai University School of Dentistry, Saitama, Japan
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HIROYASU HAYASHI
Division of Oral and Maxillofacial Surgery, Department of Diagnostic and Therapeutic Sciences, Meikai University School of Dentistry, Saitama, Japan
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AYAKO OKUYAMA
Division of Oral and Maxillofacial Surgery, Department of Diagnostic and Therapeutic Sciences, Meikai University School of Dentistry, Saitama, Japan
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JUNYA SHIONO
Division of Oral and Maxillofacial Surgery, Department of Diagnostic and Therapeutic Sciences, Meikai University School of Dentistry, Saitama, Japan
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KATSUYUKI INOUE
Division of Oral and Maxillofacial Surgery, Department of Diagnostic and Therapeutic Sciences, Meikai University School of Dentistry, Saitama, Japan
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HIDEAKI SAKASHITA
Division of Oral and Maxillofacial Surgery, Department of Diagnostic and Therapeutic Sciences, Meikai University School of Dentistry, Saitama, Japan
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Abstract

Background/Aim: This study aimed to elucidate the role of glutathione peroxidase 4 (GPX4) on the sterol regulatory element binding proteins (SREBPs)-proliferation pathway in oral cancer cells, and determine its protein expression in oral cancer tissues. Materials and Methods: Quantitative RT-PCR and immunoblot analysis were carried out. Cell viability assay, apoptosis detection assay, immunohistochemistry and GPX4 knockdown were performed. Results: The levels of both GPX4 mRNA and protein were highest in SAS cells. GPX4 knockdown in SAS cells, a human oral squamous cell carcinoma cell line, using GPX4 siRNA resulted in a reduction in cell number, which appeared to be due to non-apoptotic cell death such as ferroptosis. Furthermore, SREBP was clearly down-regulated by GPX4 knockdown in SAS cells. Immunopositivity for GPX4 was revealed on the membrane of human oral squamous cell carcinoma cells, and this was correlated with p53 immunoreactivity. Conclusion: GPX4 appears to play an important role in oral cancer proliferation.

Key Words:
  • Glutathione peroxidase 4
  • ferroptosis
  • SREBP
  • p53
  • human oral squamous cell carcinoma
  • Received January 13, 2021.
  • Revision received February 19, 2021.
  • Accepted February 22, 2021.
  • Copyright © 2021 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.
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Anticancer Research: 41 (4)
Anticancer Research
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April 2021
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Down-regulation of Glutathione Peroxidase 4 in Oral Cancer Inhibits Tumor Growth Through SREBP1 Signaling
MASAKATSU FUKUDA, YUDAI OGASAWARA, HIROYASU HAYASHI, AYAKO OKUYAMA, JUNYA SHIONO, KATSUYUKI INOUE, HIDEAKI SAKASHITA
Anticancer Research Apr 2021, 41 (4) 1785-1792; DOI: 10.21873/anticanres.14944

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Down-regulation of Glutathione Peroxidase 4 in Oral Cancer Inhibits Tumor Growth Through SREBP1 Signaling
MASAKATSU FUKUDA, YUDAI OGASAWARA, HIROYASU HAYASHI, AYAKO OKUYAMA, JUNYA SHIONO, KATSUYUKI INOUE, HIDEAKI SAKASHITA
Anticancer Research Apr 2021, 41 (4) 1785-1792; DOI: 10.21873/anticanres.14944
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Keywords

  • Glutathione peroxidase 4
  • ferroptosis
  • SREBP
  • p53
  • human oral squamous cell carcinoma
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