γ‑tocotrienol prevents 5‑FU‑induced reactive oxygen species production in human oral keratinocytes through the stabilization of 5‑FU‑induced activation of Nrf2

• 資料種別: 博士論文
• ISSN: 1019-6439
• タイトル: γ‑tocotrienol prevents 5‑FU‑induced reactive oxygen species production in human oral keratinocytes through the stabilization of 5‑FU‑induced activation of Nrf2
• 巻次・部編番号: 46 4
• 著者・編者: Takano, Hideyuki; Momota, Yukihiro; Kani, Kouichi; Aota, Keiko; Yamamura, Yoshiko; Yamanoi, Tomoko; Azuma, Masayuki
• 著者標目: Takano, Hideyuki; Momota, Yukihiro; Kani, Kouichi; Aota, Keiko; Yamamura, Yoshiko; Yamanoi, Tomoko; Azuma, Masayuki
• 出版事項: Spandidos Publications
• 出版年月日等: 2015-01-26
• 出版年（W3CDTF）: 2015-01-26
• 並列タイトル等: 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
• タイトル（掲載誌）: International Journal of Oncology
• 授与機関名: 徳島大学
• 授与年月日: 2015-02-12
• 授与年月日（W3CDTF）: 2015-02-12
• 報告番号: 甲第2807号
• 学位: 博士（歯学）
• 博論授与番号: 甲第2807号
• 本文の言語コード: eng
• 件名標目: oral keratinocytes; oral cancer; mucositis; reactive oxygen species; 5‑FU; γ‑tocotrienol; Nrf2
• 対象利用者: 一般
• 一般注記: 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.
• DOI: info:doi/10.3892/ijo.2015.2849; https://doi.org/info:doi/10.3892/ijo.2015.2849
• 国立国会図書館永続的識別子: info:ndljp/pid/9374746; https://dl.ndl.go.jp/pid/9374746
• コレクション（共通）: 障害者向け資料
• コレクション（障害者向け資料：レベル1）: テキストデータ
• コレクション（個別）: 国立国会図書館デジタルコレクション > デジタル化資料 > 博士論文; https://dl.ndl.go.jp/collections/A00014
• 収集根拠: 博士論文（自動収集）
• 受理日（W3CDTF）: 2015-06-02T13:06:44+09:00
• 記録形式（IMT）: application/pdf
• オンライン閲覧公開範囲: 国立国会図書館内限定公開
• デジタル化資料送信: 図書館・個人送信対象外
• 遠隔複写可否（NDL）: 可
• 掲載誌（URI）: http://repo.lib.tokushima-u.ac.jp/109341
• 連携機関・データベース: 国立国会図書館 : 国立国会図書館デジタルコレクション; https://dl.ndl.go.jp