Abstract Title:

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

Abstract Source:

Int J Mol Med. 2018 Nov 21. Epub 2018 Nov 21. PMID: 30483736

Abstract Author(s):

Uddin Md Nazim, Sang-Youel Park

Article Affiliation:

Uddin Md Nazim


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 increasedp62 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 combinationwith 6‑sho may be a suitable therapeutic method for the treatment of TRAIL‑resistant Huh7 liver cells.

Study Type : In Vitro Study

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