Targeting peroxiredoxin 1 impairs growth of breast cancer cells and potently sensitises these cells to prooxidant agents

Br J Cancer. 2018 Oct;119(7):873-884. doi: 10.1038/s41416-018-0263-y. Epub 2018 Oct 5.


Background: Our previous work has shown peroxiredoxin-1 (PRDX1), one of major antioxidant enzymes, to be a biomarker in human breast cancer. Hereby, we further investigate the role of PRDX1, compared to its close homolog PRDX2, in mammary malignant cells.

Methods: CRISPR/Cas9- or RNAi-based methods were used for genetic targeting PRDX1/2. Cell growth was assessed by crystal violet, EdU incorporation or colony formation assays. In vivo growth was assessed by a xenotransplantation model. Adenanthin was used to inhibit the thioredoxin-dependent antioxidant defense system. The prooxidant agents used were hydrogen peroxide, glucose oxidase and sodium L-ascorbate. A PY1 probe or HyPer-3 biosensor were used to detect hydrogen peroxide content in samples.

Results: PRDX1 downregulation significantly impaired the growth rate of MCF-7 and ZR-75-1 breast cancer cells. Likewise, xenotransplanted PRDX1-deficient MCF-7 cells presented a retarded tumour growth. Furthermore, genetic targeting of PRDX1 or adenanthin, but not PRDX2, potently sensitised all six cancer cell lines studied, but not the non-cancerous cells, to glucose oxidase and ascorbate.

Conclusions: Our study pinpoints the dominant role for PRDX1 in management of exogeneous oxidative stress by breast cancer cells and substantiates further exploration of PRDX1 as a target in this disease, especially when combined with prooxidant agents.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antioxidants / administration & dosage*
  • Antioxidants / pharmacology
  • Ascorbic Acid / administration & dosage
  • Ascorbic Acid / pharmacology
  • Breast Neoplasms / genetics
  • Breast Neoplasms / therapy*
  • CRISPR-Cas Systems
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Diterpenes, Kaurane / administration & dosage*
  • Diterpenes, Kaurane / pharmacology
  • Female
  • Gene Knockdown Techniques / methods*
  • Glucose Oxidase / administration & dosage
  • Glucose Oxidase / pharmacology
  • Humans
  • MCF-7 Cells
  • Mice
  • Oxidative Stress / drug effects
  • Peroxiredoxins / genetics*
  • RNA Interference
  • Up-Regulation / drug effects
  • Xenograft Model Antitumor Assays


  • Antioxidants
  • Diterpenes, Kaurane
  • adenanthin
  • Glucose Oxidase
  • PRDX1 protein, human
  • PRDX2 protein, human
  • Peroxiredoxins
  • Ascorbic Acid