Peroxiredoxin V Silencing Elevates Susceptibility to Doxorubicin-induced Cell Apoptosis via ROS-dependent Mitochondrial Dysfunction in AGS Gastric Cancer Cells

Anticancer Res. 2021 Apr;41(4):1831-1840. doi: 10.21873/anticanres.14949.

Abstract

Background/aim: Peroxiredoxin V (Prx V) plays crucial roles in cellular apoptosis and proliferation in various cancer cells by regulating the cellular reactive oxygen species (ROS) levels.

Materials and methods: Here, we examined the possible regulatory effects of Prx V on doxorubicin (DOX)-induced cellular apoptosis and its mechanisms in the human gastric adenocarcinoma cell line (AGS cells).

Results: Our findings suggest that Prx V knockdown may significantly increase the DOX-induced apoptosis by aggravating intracellular ROS accumulation. We also found that DOX-induced mitochondrial ROS levels and membrane permeability were significantly higher in short hairpin Prx V cells than in mock cells, and these phenomena were dramatically reversed by ROS scavenger treatment. Prx V knockdown also significantly upregulated the cleaved caspase 9, 3, and B-cell lymphoma 2 (Bcl2)-associated agonist of cell death/Bcl2 protein expression levels, suggesting that Prx V knockdown activates mitochondria-dependent apoptotic signaling pathways.

Conclusion: Taken together, this study suggests that Prx V may be a strong molecular target for gastric cancer (GC) chemotherapy, and further elucidates the role of Prx V in oxidative stress-induced cell apoptosis.

Keywords: Peroxiredoxin V; apoptosis; gastric cancer; mitochondria; reactive oxygen species.

MeSH terms

  • Adenocarcinoma / drug therapy*
  • Adenocarcinoma / enzymology
  • Adenocarcinoma / genetics
  • Adenocarcinoma / pathology
  • Antibiotics, Antineoplastic / pharmacology*
  • Apoptosis / drug effects*
  • Apoptosis Regulatory Proteins / metabolism
  • Cell Line, Tumor
  • Doxorubicin / pharmacology*
  • Gene Expression Regulation, Neoplastic
  • Gene Silencing*
  • Humans
  • Mitochondria / drug effects*
  • Mitochondria / enzymology
  • Mitochondria / pathology
  • Oxidative Stress / drug effects*
  • Peroxiredoxins / genetics
  • Peroxiredoxins / metabolism*
  • Reactive Oxygen Species / metabolism*
  • Signal Transduction
  • Stomach Neoplasms / drug therapy*
  • Stomach Neoplasms / enzymology
  • Stomach Neoplasms / genetics
  • Stomach Neoplasms / pathology

Substances

  • Antibiotics, Antineoplastic
  • Apoptosis Regulatory Proteins
  • Reactive Oxygen Species
  • Doxorubicin
  • PRDX5 protein, human
  • Peroxiredoxins