Open Access

Autophagy flux inhibition mediated by celastrol sensitized lung cancer cells to TRAIL‑induced apoptosis via regulation of mitochondrial transmembrane potential and reactive oxygen species

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

  • Published online on: December 12, 2018     https://doi.org/10.3892/mmr.2018.9757
  • Pages: 984-993
  • 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‑related apoptosis-inducing ligand (TRAIL) is well known as a transmembrane cytokine and has been proposed as one of the most effective anti‑cancer therapeutic agents, owing to its efficiency to selectively induce cell death in a variety of tumor cells. Suppression of autophagy flux has been increasingly acknowledged as an effective and novel therapeutic intervention for cancer. The present study demonstrated that the anti‑cancer and anti‑inflammatory drug celastrol, through its anti‑metastatic properties, may initiate TRAIL‑mediated apoptotic cell death in lung cancer cells. This sensitization was negatively affected by N‑acetyl‑l‑cysteine, which restored the mitochondrial membrane potential (ΔΨm) and inhibited reactive oxygen species (ROS) generation. Notably, treatment with celastrol caused an increase in microtubule‑associated proteins 1A/1B light chain 3B‑II and p62 levels, whereas co‑treatment of celastrol and TRAIL increased active caspase 3 and 8 levels compared with the control, confirming inhibited autophagy flux. The combined use of TRAIL with celastrol may serve as a safe and adequate therapeutic technique for the treatment of TRAIL‑resistant lung cancer, suggesting that celastrol‑mediated autophagy flux inhibition sensitized TRAIL‑initiated apoptosis via regulation of ROS and ΔΨm.
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February-2019
Volume 19 Issue 2

Print ISSN: 1791-2997
Online ISSN:1791-3004

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Spandidos Publications style
Nazim UM, Yin H and Park SY: Autophagy flux inhibition mediated by celastrol sensitized lung cancer cells to TRAIL‑induced apoptosis via regulation of mitochondrial transmembrane potential and reactive oxygen species. Mol Med Rep 19: 984-993, 2019.
APA
Nazim, U.M., Yin, H., & Park, S. (2019). Autophagy flux inhibition mediated by celastrol sensitized lung cancer cells to TRAIL‑induced apoptosis via regulation of mitochondrial transmembrane potential and reactive oxygen species. Molecular Medicine Reports, 19, 984-993. https://doi.org/10.3892/mmr.2018.9757
MLA
Nazim, U. M., Yin, H., Park, S."Autophagy flux inhibition mediated by celastrol sensitized lung cancer cells to TRAIL‑induced apoptosis via regulation of mitochondrial transmembrane potential and reactive oxygen species". Molecular Medicine Reports 19.2 (2019): 984-993.
Chicago
Nazim, U. M., Yin, H., Park, S."Autophagy flux inhibition mediated by celastrol sensitized lung cancer cells to TRAIL‑induced apoptosis via regulation of mitochondrial transmembrane potential and reactive oxygen species". Molecular Medicine Reports 19, no. 2 (2019): 984-993. https://doi.org/10.3892/mmr.2018.9757