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Cited by 208

The DOI matches its Crossref record; 8 of the 8 references it cites were found in a registry or an index.

Gain of Nrf2 Function in Non-Small-Cell Lung Cancer Cells Confers Radioresistance

Open access
Singh, Anju, Bodas, Manish, Wakabayashi, Nobunao, Bunz, Fred, Biswal, Shyam·2010·Antioxidants & Redox Signaling

Abstract

Nuclear factor erythroid-2 related factor 2 (Nrf2), a redox-sensitive transcription factor, regulates the expression of antioxidant enzymes and several anti-apoptotic proteins, which confer cytoprotection against oxidative stress and apoptosis. Constitutive activation of Nrf2 in lung cancer cells promotes tumorigenicity and contributes to chemoresistance by upregulation of glutathione, thioredoxin, and the drug efflux pathways involved in detoxification of electrophiles and broad spectrum of drugs. In this study, we show that RNAi-mediated lowering of Nrf2 levels in non-small-cell lung cancer (NSCLC) cell lines (A549 and H460) led to a dramatic increase in endogenous reactive oxygen species (ROS) levels. Similarly, γ-irradiation-induced formation of protein carbonyls were significantly higher in Nrf2-depleted lung cancer cells, suggesting increased lethality of ionizing radiation in the absence of Nrf2. Radiation-induced protein oxidation in Nrf2shRNA cells correlated with reduced survival as measured by clonogenic assay. Radiation-induced cell death was abrogated by pretreatment with antioxidants such as N-acetyl-L-cysteine, glutathione, and vitamin-E, highlighting the importance of antioxidants in conferring protection against radiation injury. Using genetically-modified gain and loss of function models of Nrf2, in mouse embryonic fibroblasts, we establish that constitutive activation of Nrf2 protects against ionizing radiation toxicity and confers radioresistance. Thus, targeting Nrf2 activity in radioresistant tumors could be a promising strategy to circumvent radioresistance.

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Metadata

Authors
Singh, A., Bodas, M., Wakabayashi, N., Bunz, F., & Biswal, S.
Venue
Antioxidants & Redox Signaling
Published
2010-12
Volume
13
Issue
11
Pages
1627-1637
ISSN
  • 1523-0864 (ISSN-L)
  • 1557-7716
OpenAlex
W2168973737
Cited by
208
References
8
FWCI
4.84
Type
journal article
Language
en
Open access
green

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CoChat. (2026). Citation check: Gain of Nrf2 Function in Non-Small-Cell Lung Cancer Cells Confers Radioresistance. https://app.cochat.ai/papers/10.1089/ars.2010.3219
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Singh, A., Bodas, M., Wakabayashi, N., Bunz, F., & Biswal, S. (2010). Gain of Nrf2 Function in Non-Small-Cell Lung Cancer Cells Confers Radioresistance. Antioxidants & Redox Signaling. https://doi.org/10.1089/ars.2010.3219

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