PRDX2 protects against oxidative stress induced by H. pylori and promotes resistance to cisplatin in gastric cancer

Sen Wang, Zheng Chen, Shoumin Zhu, Heng Lu, Dunfa Peng, Mohammed Soutto, Huma Naz, Richard Peek, Hao Xu, Alexander Zaika, Zekuan Xu, Wael El-Rifai

Research output: Contribution to journalArticle

Abstract

Background: Helicobacter pylori (H. pylori) infection is the main risk factor for gastric cancer. The role of antioxidant enzyme peroxiredoxin 2 (PRDX2) in gastric tumorigenesis remains unknown. In vitro (AGS and SNU-1 cell lines) and in vivo mouse models were utilized to investigate the role of PRDX2 in response to H. pylori infection (7.13, J166 or PMSS1 strain). We detected high levels of PRDX2 expression in gastric cancer tissues. Gastric cancer patients with high expression levels of PRDX2 had significantly worse overall and progression-free survival than those with low levels. H. pylori infection induced activation of NF-κB with increased expression of PRDX2, in in vitro and in vivo models. The knockdown of PRDX2 led to an increase in the levels of reactive oxygen species (ROS), oxidative DNA damage, and double-strand DNA breaks, in response to H. pylori infection, as measured by H2DCFDA, 8-oxoguanine, and p-H2AXγ assays. Luciferase reporter and ChIP assays confirmed the presence of a putative binding site of NF-κB-p65 on PRDX2 promoter region. The inhibition of PRDX2 significantly sensitized AGS and SNU-1 cells to cisplatin treatment. Our data suggest that the future development of therapeutic approaches targeting PRDX2 may be useful in the treatment of gastric cancer.

Original languageEnglish (US)
Article number101319
JournalRedox Biology
Volume28
DOIs
StatePublished - Jan 1 2020

Fingerprint

Peroxiredoxins
Oxidative stress
Helicobacter pylori
Cisplatin
Stomach Neoplasms
Oxidative Stress
Helicobacter Infections
Assays
Double-Stranded DNA Breaks
DNA
Luciferases
Genetic Promoter Regions
DNA Damage
Disease-Free Survival
Reactive Oxygen Species
Stomach
Carcinogenesis
Therapeutics
Antioxidants
Chemical activation

Keywords

  • Antioxidant response
  • Apoptosis
  • Infection
  • NF-κB
  • Oxidative DNA damage

ASJC Scopus subject areas

  • Biochemistry
  • Organic Chemistry

Cite this

PRDX2 protects against oxidative stress induced by H. pylori and promotes resistance to cisplatin in gastric cancer. / Wang, Sen; Chen, Zheng; Zhu, Shoumin; Lu, Heng; Peng, Dunfa; Soutto, Mohammed; Naz, Huma; Peek, Richard; Xu, Hao; Zaika, Alexander; Xu, Zekuan; El-Rifai, Wael.

In: Redox Biology, Vol. 28, 101319, 01.01.2020.

Research output: Contribution to journalArticle

Wang, Sen ; Chen, Zheng ; Zhu, Shoumin ; Lu, Heng ; Peng, Dunfa ; Soutto, Mohammed ; Naz, Huma ; Peek, Richard ; Xu, Hao ; Zaika, Alexander ; Xu, Zekuan ; El-Rifai, Wael. / PRDX2 protects against oxidative stress induced by H. pylori and promotes resistance to cisplatin in gastric cancer. In: Redox Biology. 2020 ; Vol. 28.
@article{e63347c8025441769a2788c257a6a478,
title = "PRDX2 protects against oxidative stress induced by H. pylori and promotes resistance to cisplatin in gastric cancer",
abstract = "Background: Helicobacter pylori (H. pylori) infection is the main risk factor for gastric cancer. The role of antioxidant enzyme peroxiredoxin 2 (PRDX2) in gastric tumorigenesis remains unknown. In vitro (AGS and SNU-1 cell lines) and in vivo mouse models were utilized to investigate the role of PRDX2 in response to H. pylori infection (7.13, J166 or PMSS1 strain). We detected high levels of PRDX2 expression in gastric cancer tissues. Gastric cancer patients with high expression levels of PRDX2 had significantly worse overall and progression-free survival than those with low levels. H. pylori infection induced activation of NF-κB with increased expression of PRDX2, in in vitro and in vivo models. The knockdown of PRDX2 led to an increase in the levels of reactive oxygen species (ROS), oxidative DNA damage, and double-strand DNA breaks, in response to H. pylori infection, as measured by H2DCFDA, 8-oxoguanine, and p-H2AXγ assays. Luciferase reporter and ChIP assays confirmed the presence of a putative binding site of NF-κB-p65 on PRDX2 promoter region. The inhibition of PRDX2 significantly sensitized AGS and SNU-1 cells to cisplatin treatment. Our data suggest that the future development of therapeutic approaches targeting PRDX2 may be useful in the treatment of gastric cancer.",
keywords = "Antioxidant response, Apoptosis, Infection, NF-κB, Oxidative DNA damage",
author = "Sen Wang and Zheng Chen and Shoumin Zhu and Heng Lu and Dunfa Peng and Mohammed Soutto and Huma Naz and Richard Peek and Hao Xu and Alexander Zaika and Zekuan Xu and Wael El-Rifai",
year = "2020",
month = "1",
day = "1",
doi = "10.1016/j.redox.2019.101319",
language = "English (US)",
volume = "28",
journal = "Redox Biology",
issn = "2213-2317",
publisher = "Elsevier BV",

}

TY - JOUR

T1 - PRDX2 protects against oxidative stress induced by H. pylori and promotes resistance to cisplatin in gastric cancer

AU - Wang, Sen

AU - Chen, Zheng

AU - Zhu, Shoumin

AU - Lu, Heng

AU - Peng, Dunfa

AU - Soutto, Mohammed

AU - Naz, Huma

AU - Peek, Richard

AU - Xu, Hao

AU - Zaika, Alexander

AU - Xu, Zekuan

AU - El-Rifai, Wael

PY - 2020/1/1

Y1 - 2020/1/1

N2 - Background: Helicobacter pylori (H. pylori) infection is the main risk factor for gastric cancer. The role of antioxidant enzyme peroxiredoxin 2 (PRDX2) in gastric tumorigenesis remains unknown. In vitro (AGS and SNU-1 cell lines) and in vivo mouse models were utilized to investigate the role of PRDX2 in response to H. pylori infection (7.13, J166 or PMSS1 strain). We detected high levels of PRDX2 expression in gastric cancer tissues. Gastric cancer patients with high expression levels of PRDX2 had significantly worse overall and progression-free survival than those with low levels. H. pylori infection induced activation of NF-κB with increased expression of PRDX2, in in vitro and in vivo models. The knockdown of PRDX2 led to an increase in the levels of reactive oxygen species (ROS), oxidative DNA damage, and double-strand DNA breaks, in response to H. pylori infection, as measured by H2DCFDA, 8-oxoguanine, and p-H2AXγ assays. Luciferase reporter and ChIP assays confirmed the presence of a putative binding site of NF-κB-p65 on PRDX2 promoter region. The inhibition of PRDX2 significantly sensitized AGS and SNU-1 cells to cisplatin treatment. Our data suggest that the future development of therapeutic approaches targeting PRDX2 may be useful in the treatment of gastric cancer.

AB - Background: Helicobacter pylori (H. pylori) infection is the main risk factor for gastric cancer. The role of antioxidant enzyme peroxiredoxin 2 (PRDX2) in gastric tumorigenesis remains unknown. In vitro (AGS and SNU-1 cell lines) and in vivo mouse models were utilized to investigate the role of PRDX2 in response to H. pylori infection (7.13, J166 or PMSS1 strain). We detected high levels of PRDX2 expression in gastric cancer tissues. Gastric cancer patients with high expression levels of PRDX2 had significantly worse overall and progression-free survival than those with low levels. H. pylori infection induced activation of NF-κB with increased expression of PRDX2, in in vitro and in vivo models. The knockdown of PRDX2 led to an increase in the levels of reactive oxygen species (ROS), oxidative DNA damage, and double-strand DNA breaks, in response to H. pylori infection, as measured by H2DCFDA, 8-oxoguanine, and p-H2AXγ assays. Luciferase reporter and ChIP assays confirmed the presence of a putative binding site of NF-κB-p65 on PRDX2 promoter region. The inhibition of PRDX2 significantly sensitized AGS and SNU-1 cells to cisplatin treatment. Our data suggest that the future development of therapeutic approaches targeting PRDX2 may be useful in the treatment of gastric cancer.

KW - Antioxidant response

KW - Apoptosis

KW - Infection

KW - NF-κB

KW - Oxidative DNA damage

UR - http://www.scopus.com/inward/record.url?scp=85072179179&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85072179179&partnerID=8YFLogxK

U2 - 10.1016/j.redox.2019.101319

DO - 10.1016/j.redox.2019.101319

M3 - Article

C2 - 31536951

AN - SCOPUS:85072179179

VL - 28

JO - Redox Biology

JF - Redox Biology

SN - 2213-2317

M1 - 101319

ER -