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

• Material Type: 博士論文
• Title: γ‑tocotrienol prevents 5‑FU‑induced reactive oxygen species production in human oral keratinocytes through the stabilization of 5‑FU‑induced activation of Nrf2
• Author/Editor: Takano, Hideyuki; Momota, Yukihiro; Kani, Kouichi; Aota, Keiko; Yamamura, Yoshiko; Yamanoi, Tomoko; Azuma, Masayuki
• Author Heading: Takano, Hideyuki; Momota, Yukihiro; Kani, Kouichi; Aota, Keiko; Yamamura, Yoshiko; Yamanoi, Tomoko; Azuma, Masayuki
• Publication, Distribution, etc.: Spandidos Publications
• Publication Date: 2015-01-26
• Publication Date (W3CDTF): 2015-01-26
• Alternative Title: 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
• Periodical title: International Journal of Oncology
• No. or year of volume/issue: 46 4
• Volume: 46
• Issue: 4
• Pages: 1453-1460
• ISSN (Periodical Title): ISSN : 1019-6439; ISSN : 1791-2423
• Degree grantor/type: 徳島大学
• Date Granted: 2015-02-12
• Dissertation Number: 甲第2807号
• Degree Type: 博士（歯学）
• Text Language Code: eng
• Subject Heading: oral keratinocytes; oral cancer; mucositis; reactive oxygen species; 5‑FU; γ‑tocotrienol; Nrf2
• Target Audience: 一般
• Note (General): 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.
• Format (IMT): application/pdf
• Access Restrictions: インターネット公開
• Rights (production): 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/ )
• Related Material (DOI): 10.3892/ijo.2015.2849
• Data Provider (Database): 国立情報学研究所 : 学術機関リポジトリデータベース（IRDB）（機関リポジトリ）; https://irdb.nii.ac.jp
• Original Data Provider (Database): 徳島大学 : 徳島大学機関リポジトリ

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