Gomisin N enhances TRAIL-induced apoptosis via reactive oxygen species-mediated up-regulation of death receptors 4 and 5

  • Authors:
    • Hiroki Inoue
    • Pornthip Waiwut
    • Ikuo Saiki
    • Yutaka Shimada
    • Hiroaki Sakurai
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  • Published online on: December 15, 2011     https://doi.org/10.3892/ijo.2011.1299
  • Pages: 1058-1065
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Abstract

Pharmacological studies have revealed that lignans isolated from Schisandra chinensis, including gomisin N, show anticancer, anti-hepatotoxic, anti-oxidative and anti-inflammatory activities. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is an important member of the tumor necrosis factor superfamily with great potential in cancer therapy. The present study investigated whether pretreatment with gomisin N significantly enhanced TRAIL-induced cleavage of caspase-3, caspase-8 and PARP-1, which are key markers of apoptosis. Pretreatment with z-VAD-FMK, a pan-caspase inhibitor, was able to inhibit apoptosis enhanced by the combination of gomisin N and TRAIL. These results suggested that gomisin N could promote TRAIL-induced apoptosis through the caspase cascade. In search of the molecular mechanisms, we elucidated that such enhancement was achieved through transcriptional up-regulation of TRAIL receptors, death receptor 4 (DR4) and DR5. Neutralization of DR4 and DR5 could significantly reduce apoptosis induced by gomisin N and TRAIL. We also revealed that gomisin N increased the generation of reactive oxygen species (ROS). N-acetyl cysteine (NAC), an antioxidant, could inhibit ROS production and up-regulation of DR4 and DR5. Overall, our results indicated that gomisin N was able to potentiate TRAIL-induced apoptosis through ROS-mediated up-regulation of DR4 and DR5.
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April 2012
Volume 40 Issue 4

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Spandidos Publications style
Inoue H, Waiwut P, Saiki I, Shimada Y and Sakurai H: Gomisin N enhances TRAIL-induced apoptosis via reactive oxygen species-mediated up-regulation of death receptors 4 and 5. Int J Oncol 40: 1058-1065, 2012
APA
Inoue, H., Waiwut, P., Saiki, I., Shimada, Y., & Sakurai, H. (2012). Gomisin N enhances TRAIL-induced apoptosis via reactive oxygen species-mediated up-regulation of death receptors 4 and 5. International Journal of Oncology, 40, 1058-1065. https://doi.org/10.3892/ijo.2011.1299
MLA
Inoue, H., Waiwut, P., Saiki, I., Shimada, Y., Sakurai, H."Gomisin N enhances TRAIL-induced apoptosis via reactive oxygen species-mediated up-regulation of death receptors 4 and 5". International Journal of Oncology 40.4 (2012): 1058-1065.
Chicago
Inoue, H., Waiwut, P., Saiki, I., Shimada, Y., Sakurai, H."Gomisin N enhances TRAIL-induced apoptosis via reactive oxygen species-mediated up-regulation of death receptors 4 and 5". International Journal of Oncology 40, no. 4 (2012): 1058-1065. https://doi.org/10.3892/ijo.2011.1299