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ID 109341
タイトル別表記
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
著者
高野, 栄之 徳島大学大学院口腔科学教育部(口腔科学専攻) 徳島大学 教育研究者総覧 KAKEN研究者をさがす
キーワード
oral keratinocytes
oral cancer
mucositis
reactive oxygen species
5‑FU
γ‑tocotrienol
Nrf2
資料タイプ
学位論文
抄録
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.
掲載誌名
International Journal of Oncology
ISSN
10196439
17912423
cat書誌ID
AA10992511
出版者
Spandidos Publications
46
4
開始ページ
1453
終了ページ
1460
発行日
2015-01-26
備考
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。
権利情報
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
出版社版DOI
出版社版URL
フルテキストファイル
言語
eng
著者版フラグ
博士論文全文を含む
文科省報告番号
甲第2807号
学位記番号
甲口第389号
学位授与年月日
2015-02-12
学位名
博士(歯学)
学位授与機関
徳島大学
部局
病院
歯学系