1. Targeting peroxiredoxin 1 impairs growth of breast cancer cells and potently sensitises these cells to prooxidant agents
- Author
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Bajor, Malgorzata, Zych, Agata O, Graczyk-Jarzynka, Agnieszka, Muchowicz, Angelika, Firczuk, Malgorzata, Trzeciak, Lech, Gaj, Pawel, Domagala, Antoni, Siernicka, Marta, Zagozdzon, Agnieszka, Siedlecki, Pawel, Kniotek, Monika, O’Leary, Patrick C, Golab, Jakub, and Zagozdzon, Radoslaw
- Subjects
Biomedical and Clinical Sciences ,Oncology and Carcinogenesis ,Breast Cancer ,Cancer ,Animals ,Antioxidants ,Ascorbic Acid ,Breast Neoplasms ,CRISPR-Cas Systems ,Cell Line ,Tumor ,Cell Proliferation ,Diterpenes ,Kaurane ,Female ,Gene Knockdown Techniques ,Glucose Oxidase ,Humans ,MCF-7 Cells ,Mice ,Oxidative Stress ,Peroxiredoxins ,RNA Interference ,Up-Regulation ,Xenograft Model Antitumor Assays ,Public Health and Health Services ,Oncology & Carcinogenesis ,Oncology and carcinogenesis - Abstract
BackgroundOur 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.MethodsCRISPR/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.ResultsPRDX1 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.ConclusionsOur 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.
- Published
- 2018