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 accessAbstract
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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Cites
Cell Survival Responses to Environmental Stresses Via the Keap1-Nrf2-ARE Pathway
Kensler, T. W., Wakabayashi, N., & Biswal, S. (2007) · Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev.pharmtox.46.120604.141046 · Cited by 3,630
Self-citationAssociation of reactive oxygen species levels and radioresistance in cancer stem cells
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Dysfunctional KEAP1–NRF2 Interaction in Non-Small-Cell Lung Cancer
Singh, A., Misra, V., Thimmulappa, R. K., Lee, H., Ames, S., Hoque, M. O., Herman, J. G., Baylin, S. B., Sidransky, D., Gabrielson, E., et al. (2006) · PLoS Medicine · doi:10.1371/journal.pmed.0030420 · Cited by 1,060
Self-citationStructural basis for defects of Keap1 activity provoked by its point mutations in lung cancer
Padmanabhan, B., Tong, K. I., Ohta, T., Nakamura, Y., Scharlock, M., Ohtsuji, M., Kang, M.-I., Kobayashi, A., Yokoyama, S., & Yamamoto, M. (2006) · Molecular Cell · doi:10.1016/j.molcel.2006.01.013 · Cited by 735 · cited 3×
“Loss of Keap1 activity leading to gain of Nrf2 function in lung cancer cells upregulates the expression of cytoprotective antioxidants and anti-apoptotic proteins (21, 30).”
Disruption of Nrf2 enhances susceptibility to severe airway inflammation and asthma in mice
Rangasamy, T., Guo, J., Mitzner, W. A., Roman, J., Singh, A., Fryer, A. D., Yamamoto, M., Kensler, T. W., Tuder, R. M., Georas, S. N., et al. (2005) · The Journal of Experimental Medicine · doi:10.1084/jem.20050538 · Cited by 580
Self-citationA mutation of Keap1 found in breast cancer impairs its ability to repress Nrf2 activity
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Genetic alterations defining NSCLC subtypes and their therapeutic implications
Pikor, L. A., Ramnarine, V. R., Lam, S., & Lam, W. L. (2013) · Lung Cancer · doi:10.1016/j.lungcan.2013.07.025 · Cited by 375
Transcription factor NRF2 regulates miR-1 and miR-206 to drive tumorigenesis
Singh, A., Happel, C., Manna, S. K., Acquaah-Mensah, G., Carrerero, J., Kumar, S., Nasipuri, P., Krausz, K. W., Wakabayashi, N., Dewi, R., et al. (2013) · Journal of Clinical Investigation · doi:10.1172/jci66353 · Cited by 333
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The Role of Inflammation in Cancer: Mechanisms of Tumor Initiation, Progression, and Metastasis
Nishida, A., & Andoh, A. (2025) · Cells · doi:10.3390/cells14070488 · Cited by 270
Metadata
- Authors
- Singh, A., Bodas, M., Wakabayashi, N., Bunz, F., & Biswal, S.
- Venue
- Antioxidants & Redox Signaling
- Publisher
- SAGE Publications
- 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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