徳島大学 教育・研究者情報データベース(EDB)

1. 高野 栄之

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2. 桃田 幸弘([徳島大学.大学院医歯薬学研究部.歯学域.口腔科学部門.臨床歯学系.口腔内科学]/[徳島大学.病院.診療科.歯科口腔外科.口腔内科])

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3. 可児 耕一([徳島大学.病院.診療科.歯科口腔外科.口腔内科])

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4. 青田 桂子([徳島大学.病院.診療科.歯科口腔外科.口腔内科])

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5. 山村 佳子

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6. (英) Tomoko Yamanoi / (日) 山ノ井 朋子

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7. 東 雅之

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

(英) 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 RT7 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 ROS gene rated by 5 FU treatment, because N acetyl cysteine (NAC), a ROS scavenger, significantly ameliorated the growth of RT7 cells. γ tocotrienol showed no cytotoxic effect on the growth of RT7 cells. Simultaneous treatment of cells with these agents resulted in the significant recovery of cell growth, owing to the suppression of ROS 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 RT7 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.

1. (英) Article.ELocationID: 10.3892/ijo.2015.2849

2. (英) Article.PublicationTypeList.PublicationType: Journal Article

3. (英) Article.PublicationTypeList.PublicationType: Research Support, Non-U.S. Gov't

4. (英) OtherID: PMC4356501