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

  • Authors:
    • Hideyuki Takano
    • Yukihiro Momota
    • Kouichi Kani
    • Keiko Aota
    • Yoshiko Yamamura
    • Tomoko Yamanoi
    • Masayuki Azuma
  • View Affiliations / Copyright

    Affiliations: Department of Oral Medicine, Institute of Health Biosciences, The University of Tokushima Graduate Faculty of Dentistry, Tokushima, Japan
    Copyright: © Takano et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].
  • Pages: 1453-1460
    |
    Published online on: January 26, 2015
       https://doi.org/10.3892/ijo.2015.2849
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Abstract

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 gene­rated 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.
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Copy and paste a formatted citation
Spandidos Publications style
Takano H, Momota Y, Kani K, Aota K, Yamamura Y, Yamanoi T and Azuma M: γ‑tocotrienol prevents 5‑FU‑induced reactive oxygen species production in human oral keratinocytes through the stabilization of 5‑FU‑induced activation of Nrf2. Int J Oncol 46: 1453-1460, 2015.
APA
Takano, H., Momota, Y., Kani, K., Aota, K., Yamamura, Y., Yamanoi, T., & Azuma, M. (2015). γ‑tocotrienol prevents 5‑FU‑induced reactive oxygen species production in human oral keratinocytes through the stabilization of 5‑FU‑induced activation of Nrf2. International Journal of Oncology, 46, 1453-1460. https://doi.org/10.3892/ijo.2015.2849
MLA
Takano, H., Momota, Y., Kani, K., Aota, K., Yamamura, Y., Yamanoi, T., Azuma, M."γ‑tocotrienol prevents 5‑FU‑induced reactive oxygen species production in human oral keratinocytes through the stabilization of 5‑FU‑induced activation of Nrf2". International Journal of Oncology 46.4 (2015): 1453-1460.
Chicago
Takano, H., Momota, Y., Kani, K., Aota, K., Yamamura, Y., Yamanoi, T., Azuma, M."γ‑tocotrienol prevents 5‑FU‑induced reactive oxygen species production in human oral keratinocytes through the stabilization of 5‑FU‑induced activation of Nrf2". International Journal of Oncology 46, no. 4 (2015): 1453-1460. https://doi.org/10.3892/ijo.2015.2849
Copy and paste a formatted citation
x
Spandidos Publications style
Takano H, Momota Y, Kani K, Aota K, Yamamura Y, Yamanoi T and Azuma M: γ‑tocotrienol prevents 5‑FU‑induced reactive oxygen species production in human oral keratinocytes through the stabilization of 5‑FU‑induced activation of Nrf2. Int J Oncol 46: 1453-1460, 2015.
APA
Takano, H., Momota, Y., Kani, K., Aota, K., Yamamura, Y., Yamanoi, T., & Azuma, M. (2015). γ‑tocotrienol prevents 5‑FU‑induced reactive oxygen species production in human oral keratinocytes through the stabilization of 5‑FU‑induced activation of Nrf2. International Journal of Oncology, 46, 1453-1460. https://doi.org/10.3892/ijo.2015.2849
MLA
Takano, H., Momota, Y., Kani, K., Aota, K., Yamamura, Y., Yamanoi, T., Azuma, M."γ‑tocotrienol prevents 5‑FU‑induced reactive oxygen species production in human oral keratinocytes through the stabilization of 5‑FU‑induced activation of Nrf2". International Journal of Oncology 46.4 (2015): 1453-1460.
Chicago
Takano, H., Momota, Y., Kani, K., Aota, K., Yamamura, Y., Yamanoi, T., Azuma, M."γ‑tocotrienol prevents 5‑FU‑induced reactive oxygen species production in human oral keratinocytes through the stabilization of 5‑FU‑induced activation of Nrf2". International Journal of Oncology 46, no. 4 (2015): 1453-1460. https://doi.org/10.3892/ijo.2015.2849
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