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Targeting Peroxiredoxin 1 Impairs Growth of Breast Cancer Cells and Potently Sensitises These Cells to Prooxidant Agents

Targeting Peroxiredoxin 1 Impairs Growth of Breast Cancer Cells and Potently Sensitises These Cells to Prooxidant Agents

Malgorzata Bajor, Agata O Zych, Agnieszka Graczyk-Jarzynka, Angelika Muchowicz, Malgorzata Firczuk, Lech Trzeciak, Pawel Gaj, Antoni Domagala, Marta Siernicka, Agnieszka Zagozdzon, Pawel Siedlecki, Monika Kniotek, etc.

Br J Cancer. 2018 Oct;119(7):873-884.

PMID: 30287919

Abstract:

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.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP1224696723	PY1		1224696-72-3	Price

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