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Title 

Peroxiredoxin I contributes to TRAIL resistance through suppression of redox-sensitive caspase activation in human hepatoma cells

Authors 

In-Seong SongSun-Uk KimNang-Su OhJ KimDae Yeul YuS M HuangJ M KimD S LeeNam-Soon Kim

Publisher 

Oxford University Press (OUP)

Issue Date 

2009

Citation 

Carcinogenesis, vol. 30, no. 7, pp. 1106-1114

Abstract 

Reactive oxygen species (ROS) have been implicated in tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) resistance of many cancers. We evaluated the role of peroxiredoxin (Prx) I in TRAIL resistance governed by coupling of nicotinamide adenosine dinucleotide phosphate oxidase (Nox)-derived ROS signaling with the p38 mitogen-activated protein kinase (MAPK)/caspase-signaling cascade in liver cancer cells. Upregulated Prx I expression was found in neoplastic regions of human patient liver, and Prx I knockdown resulted in accelerated TRAIL-induced cell death in SK-Hep-1 human hepatoma cells. The TRAIL cytotoxicity by Prx I knockdown was dependent on activation of caspase-8/3 cascades, which was ablated by addition of inhibitors for p38 MAPK, ROS or Nox, suggesting the association with Nox-driven redox signaling. Furthermore, we found that Nox4 was constitutively expressed in both SK-Hep-1 cells and tumor regions of patient livers, knockdown of Nox4 expression could alleviate ROS generation and TRAIL-mediated cytotoxicity. In accordance with previous findings, increased activation of both p38 MAPK and caspase cascades by Prx I knockdown was inhibited by either Nox4 knockdown or SB203580 addition. Collectively, these data suggest that Prx I functions to block propagation of Nox-derived ROS signaling to the p38 MAPK/caspase/cell death cascade during TRAIL treatment and also provides a molecular mechanism by which Prx I contributes to TRAIL resistance in liver cancers.

ISSN 

0143-3334

Link 

http://dx.doi.org/10.1093/carcin/bgp104

Appears in Collections

1. Journal Articles > Journal Articles

Registered Date

2017-04-19


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