Open Access

γ-tocotrienol enhances the chemosensitivity of human oral cancer cells to docetaxel through the downregulation of the expression of NF-κB-regulated anti-apoptotic gene products

  • Authors:
    • Kouichi Kani
    • Yukihiro Momota
    • Michito Harada
    • Yoshiko Yamamura
    • Keiko  Aota
    • Tomoko Yamanoi
    • Hideyuki Takano
    • Katsumi Motegi
    • Masayuki Azuma
  • View Affiliations

  • Published online on: November 8, 2012     https://doi.org/10.3892/ijo.2012.1692
  • Pages: 75-82
  • Copyright: © Kani et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].

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Abstract

Taxanes, including docetaxel, are widely used for the treatment of squamous cell carcinoma of the head and neck. However, the gastrointestinal toxicity of docetaxel has limited its high-dose clinical use. In this study, we examined the synergistic anticancer effects of combined low-dose docetaxel and γ-tocotrienol treatment on human oral cancer (B88) cells. We treated B88 cells with docetaxel and γ-tocotrienol at concentrations of 0.5 nM and 50 µM, respectively. When cells were treated with either agent alone at a low dose, no significant cytotoxic effect was observed. However, the simultaneous treatment of cells with both agents almost completely suppressed cell growth. Whereas docetaxel stimulated the expression of nuclear factor-κB (NF-κB) p65 protein in B88 cells, γ-tocotrienol slightly inhibited the expression of constitutive nuclear p65 protein. Of note, the combined treatment with both agents inhibited docetaxel-induced nuclear p65 protein expression. Electrophoretic mobility shift assay (EMSA) revealed that the simultaneous treatment with these agents suppressed the NF-κB DNA binding activity in B88 cells. In addition, γ-tocotrienol downregulated the docetaxel-induced expression of NF-κB-regulated gene products associated with the inhibition of apoptosis. Furthermore, the activation of initiator caspases, caspases-8 and -9, and the effector caspase, caspase-3, was detected following treatment with both agents. Finally, apoptosis was also clearly observed as demonstrated by the cleavage of poly(ADP-ribose) polymerase (PARP) and nuclear fragmentation through the activation of caspase-3 by combined treatment with docetaxel and γ-tocotrienol. These findings suggest that the combination treatment with these agents may provide enhanced therapeutic response in oral cancer patients, while avoiding the toxicity associated with high-dose β-tubulin stabilization monotherapy.
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January 2013
Volume 42 Issue 1

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Spandidos Publications style
Kani K, Momota Y, Harada M, Yamamura Y, Aota K, Yamanoi T, Takano H, Motegi K and Azuma M: γ-tocotrienol enhances the chemosensitivity of human oral cancer cells to docetaxel through the downregulation of the expression of NF-κB-regulated anti-apoptotic gene products. Int J Oncol 42: 75-82, 2013.
APA
Kani, K., Momota, Y., Harada, M., Yamamura, Y., Aota, K., Yamanoi, T. ... Azuma, M. (2013). γ-tocotrienol enhances the chemosensitivity of human oral cancer cells to docetaxel through the downregulation of the expression of NF-κB-regulated anti-apoptotic gene products. International Journal of Oncology, 42, 75-82. https://doi.org/10.3892/ijo.2012.1692
MLA
Kani, K., Momota, Y., Harada, M., Yamamura, Y., Aota, K., Yamanoi, T., Takano, H., Motegi, K., Azuma, M."γ-tocotrienol enhances the chemosensitivity of human oral cancer cells to docetaxel through the downregulation of the expression of NF-κB-regulated anti-apoptotic gene products". International Journal of Oncology 42.1 (2013): 75-82.
Chicago
Kani, K., Momota, Y., Harada, M., Yamamura, Y., Aota, K., Yamanoi, T., Takano, H., Motegi, K., Azuma, M."γ-tocotrienol enhances the chemosensitivity of human oral cancer cells to docetaxel through the downregulation of the expression of NF-κB-regulated anti-apoptotic gene products". International Journal of Oncology 42, no. 1 (2013): 75-82. https://doi.org/10.3892/ijo.2012.1692