1. Breast cancer susceptibility gene 1 regulates oxidative damage via nuclear factor erythroid 2-related factor 2 in oral cancer cells.
- Author
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Yu X, Liu Y, Pan K, Sun P, Li J, Li L, Chen Q, and Sun Z
- Subjects
- 8-Hydroxy-2'-Deoxyguanosine genetics, 8-Hydroxy-2'-Deoxyguanosine metabolism, Apoptosis genetics, Female, Humans, Isothiocyanates pharmacology, Sulfoxides pharmacology, BRCA1 Protein genetics, Mouth Neoplasms genetics, Mouth Neoplasms metabolism, NF-E2-Related Factor 2 genetics, NF-E2-Related Factor 2 metabolism, Oxidative Stress genetics, Squamous Cell Carcinoma of Head and Neck genetics
- Abstract
Objective: To determine whether the breast cancer susceptibility gene 1 (BRCA1) regulates oxidative damage in oral cancer cells by interacting with nuclear factor erythroid 2-like 2 (NRF2)., Design: The BRCA1 gene was silenced in CAL-27 and DOK cells using specific shRNA, and NRF2 was activated with sulforaphane. The expression levels of BRCA1, NRF2 and its target genes were assessed by quantitative real-time polymerase chain reaction and western blotting. Cell counting kit-8 assay was used to detect cell proliferation, apoptosis was detected by flow cytometry, and 8-OXo-2'-deoxyguanosine level was measured by enzyme-linked immunosorbent assay. The expression of BRCA1 and NRF2 in patients with oral leukoplakia and oral squamous cell carcinoma were evaluated by immunohistochemistry., Results: BRCA1 knockdown downregulated NRF2 and its target genes, increased proliferation rates, reduced apoptosis, and increased 8-OXo-2'-deoxyguanosine levels compared to the control. Activation of NRF2 by sulforaphane significantly upregulated NRF2 levels in the BRCA1-depleted cells, and restored proliferation, apoptosis and 8-OXo-2'-deoxyguanosine level in a dose-dependent manner. Compared with patients with leukoplakia, BRCA1 and NRF2 expression were increased in patients with oral squamous cell carcinoma., Conclusions: BRCA1 depletion increases oxidative damage and promotes the malignant phenotype, which may eventually promote oral carcinogenesis. The NRF2-activator sulforaphane is a potential chemo-preventive agent for oral cancer., (Copyright © 2022 Elsevier Ltd. All rights reserved.)
- Published
- 2022
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