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Triple Combination of Ascorbate, Menadione and the Inhibition of Peroxiredoxin-1 Produces Synergistic Cytotoxic Effects in Triple-Negative Breast Cancer Cells
- Source :
- Antioxidants, Vol 9, Iss 320, p 320 (2020), Antioxidants, Volume 9, Issue 4
- Publication Year :
- 2020
- Publisher :
- MDPI AG, 2020.
-
Abstract
- Triple-negative breast cancer (TNBC) is an aggressive form of mammary malignancy currently without satisfactory systemic treatment options. Agents generating reactive oxygen species (ROS), such as ascorbate (Asc) and menadione (Men), especially applied in combination, have been proposed as an alternative anticancer modality. However, their effectiveness can be hampered by the cytoprotective effects of elevated antioxidant enzymes (e.g., peroxiredoxins, PRDX) in cancer. In this study, PRDX1 mRNA and protein expression were assessed in TNBC tissues by analysis of the online RNA-seq datasets and immunohistochemical staining of tissue microarray, respectively. We demonstrated that PRDX1 mRNA expression was markedly elevated in primary TNBC tumors as compared to non-malignant controls, with PRDX1 protein staining intensity correlating with favorable survival parameters. Subsequently, PRDX1 functionality in TNBC cell lines or non-malignant mammary cells was targeted by genetic silencing or chemically by auranofin (AUR). The PRDX1-knockdown or AUR treatment resulted in inhibition of the growth of TNBC cells in vitro. These cytotoxic effects were further synergistically potentiated by the incubation with a combination of the prooxidant agents, Asc and Men. In conclusion, we report that the PRDX1-related antioxidant system is essential for maintaining redox homeostasis in TNBC cells and can be an attractive therapeutic target in combination with ROS-generating agents.
- Subjects :
- 0301 basic medicine
antioxidant enzyme
Auranofin
Physiology
Clinical Biochemistry
Peroxiredoxin 1
Biochemistry
Article
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
Menadione
medicine
Cytotoxic T cell
Gene silencing
Molecular Biology
Triple-negative breast cancer
chemistry.chemical_classification
Reactive oxygen species
prooxidant agents
Chemistry
lcsh:RM1-950
Cancer
Cell Biology
augmented prooxidant therapy
medicine.disease
lcsh:Therapeutics. Pharmacology
030104 developmental biology
030220 oncology & carcinogenesis
triple therapeutic combination
triple-negative breast cancer
Cancer research
medicine.drug
Subjects
Details
- ISSN :
- 20763921
- Volume :
- 9
- Database :
- OpenAIRE
- Journal :
- Antioxidants
- Accession number :
- edsair.doi.dedup.....e6c65378b8642a7b600ca2696a835987