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ID 109341
Title Alternative
γ‑トコトリエノールは5‑FUにより誘導されるNrf2を安定化させることにより5‑FUによる口腔粘膜上皮細胞の活性酸素産生を抑制する
PREVENTION OF ROS GENERATION VIA STABILIZATION OF Nrf2 ACTIVATION
Author
Yamanoi, Tomoko The University of Tokushima
Azuma, Masayuki The University of Tokushima KAKEN Search Researchers
Keywords
oral keratinocytes
oral cancer
mucositis
reactive oxygen species
5‑FU
γ‑tocotrienol
Nrf2
Content Type
Thesis or Dissertation
Description
Chemotherapy‑induced oral mucositis is a common adverse event in patients with oral squamous cell carcinoma, and is initiated through a variety of mechanisms, including the generation of reactive oxygen species (ROS). In this study, we examined the preventive effect of γ‑tocotrienol on the 5‑FU‑induced ROS production in human oral keratinocytes (RT7). We treated RT 7 cells with 5‑FU and γ‑tocotrienol at concentrations of 10 μg/ml and 10 nM, respectively. When cells were treated with 5‑FU alone, significant growth inhibition was observed as compared to untreated cells. This inhibition was, in part, due to the RO S generated by 5‑FU treatment, because N‑acetyl cysteine (NAC), a RO S scavenger, significantly ameliorated the growth of RT7 cells. γ‑tocotrienol showed no cytotoxic effect on the growth of RT 7 cells. Simultaneous treatment of cells with these agents resulted in the significant recovery of cell growth, owing to the suppression of RO S generation by γ‑tocotrienol. Whereas 5‑FU stimulated the expression of NF‑E2‑related factor 2 (Nrf2) protein in the nucleus up to 12 h after treatment of RT 7 cells, γ‑tocotrienol had no obvious effect on the expression of nuclear Nrf2 protein. Of note, the combined treatment with both agents stabilized the 5‑FU‑induced nuclear Nrf2 protein expression until 24 h after treatment. In addition, expression of Nrf2‑dependent antioxidant genes, such as heme oxygenase‑1 (HO‑1) and NAD(P)H:quinone oxidoreductase‑1 (NQO‑1), was significantly augmented by treatment of cells with both agents. These findings suggest that γ‑tocotrienol could prevent 5‑FU ‑induced ROS generation by stabilizing Nrf2 activation, thereby leading to ROS detoxification and cell survival in human oral keratinocytes.
Journal Title
International Journal of Oncology
ISSN
10196439
17912423
NCID
AA10992511
Publisher
Spandidos Publications
Volume
46
Issue
4
Start Page
1453
End Page
1460
Published Date
2015-01-26
Remark
内容要旨・審査要旨・論文本文の公開:
内容要旨 : LID201505071002.pdf
審査要旨 : LID201505071003.pdf
論文本文 : LID201505071004.pdf
本論文は, 著者Hideyuki Takanoの学位論文として提出され, 学位審査・授与の対象となっている。
Rights
Copyright: © Takano et al. This is an open access article distributed under the terms of a Creative Commons Attribution License [CC BY_NC 3.0]. ( https://creativecommons.org/licenses/by-nc/3.0/ )
EDB ID
DOI (Published Version)
URL ( Publisher's Version )
FullText File
language
eng
TextVersion
ETD
MEXT report number
甲第2807号
Diploma Number
甲口第389号
Granted Date
2015-02-12
Degree Name
Doctor of Dental Science
Grantor
Tokushima University
departments
University Hospital
Oral Sciences