Open Access

Attenuation of autophagy flux by 6-shogaol sensitizes human liver cancer cells to TRAIL-induced apoptosis via p53 and ROS

  • Authors:
    • Uddin Md. Nazim
    • Sang‑Youel Park
  • View Affiliations

  • Published online on: November 21, 2018     https://doi.org/10.3892/ijmm.2018.3994
  • Pages: 701-708
  • Copyright: © Nazim et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Tumor necrosis factor (TNF)‑related apoptosis‑inducing ligand (TRAIL) is a member of the TNF superfamily and is an antitumor drug that induces apoptosis in tumor cells with minimal or no effects on normal cells. Here, it is demonstrated that 6‑shogaol (6‑sho), a bioactive component of ginger, exerted anti‑inflammatory and anticancer properties, attenuated tumor cell propagation and induced TRAIL‑mediated cell death in liver cancer cells. The current study identified a potential pathway by revealing that TRAIL and 6‑sho or chloroquine acted together to trigger reactive oxygen species (ROS) production, to upregulate tumor‑suppressor protein 53 (p53) expression and to change the mitochondrial transmembrane potential (MTP). Treatment with N‑acetyl‑L‑cysteine reversed these effects, restoring the MTP and attenuated ROS production and p53 expression. Interestingly, treatment with 6‑sho increased p62 and microtubule‑associated proteins 1A/1B light chain 3B‑II levels, indicating an inhibited autophagy flux. In conclusion, attenuation of 6‑sho‑induced autophagy flux sensitized cells to TRAIL‑induced apoptosis via p53 and ROS, suggesting that the administration of TRAIL in combination with 6‑sho may be a suitable therapeutic method for the treatment of TRAIL‑resistant Huh7 liver cells.
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February-2019
Volume 43 Issue 2

Print ISSN: 1107-3756
Online ISSN:1791-244X

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Spandidos Publications style
Nazim UM and Nazim UM: Attenuation of autophagy flux by 6-shogaol sensitizes human liver cancer cells to TRAIL-induced apoptosis via p53 and ROS. Int J Mol Med 43: 701-708, 2019
APA
Nazim, U.M., & Nazim, U.M. (2019). Attenuation of autophagy flux by 6-shogaol sensitizes human liver cancer cells to TRAIL-induced apoptosis via p53 and ROS. International Journal of Molecular Medicine, 43, 701-708. https://doi.org/10.3892/ijmm.2018.3994
MLA
Nazim, U. M., Park, S."Attenuation of autophagy flux by 6-shogaol sensitizes human liver cancer cells to TRAIL-induced apoptosis via p53 and ROS". International Journal of Molecular Medicine 43.2 (2019): 701-708.
Chicago
Nazim, U. M., Park, S."Attenuation of autophagy flux by 6-shogaol sensitizes human liver cancer cells to TRAIL-induced apoptosis via p53 and ROS". International Journal of Molecular Medicine 43, no. 2 (2019): 701-708. https://doi.org/10.3892/ijmm.2018.3994