Non-small cell lung cancer (NSCLC) cells often possess a hypermethylated Keap1 promoter, which decreases Keap1 mRNA and protein expression levels, thus impairing the Nrf2-Keap1 pathway and thereby leading to chemo- or radio-resistance.
Nrf2, a redox-sensing transcription factor, on constitutive activation in non-small-cell lung cancer cells upregulates a wide spectrum of genes involved in redox balance, glutathione metabolism, and drug detoxification, which contribute to chemoresistance and tumorigenicity.
Nrf2 is often constitutively activated in non-small cell lung cancer (NSCLC) cell lines, which promotes cytoprotection against oxidative stress and xenobiotics.
Collectively, mutant p53 may confer cisplatin resistance via upregulation of Nrf2 expression, and Nrf2 mRNA level may predict chemotherapeutic response and outcomes in NSCLC.
Erastin and APAP promoted NSCLC cell death by regulating nucleus translocation of nuclear factor erythroid 2-related factor 2 (Nrf2); and the ferroptosis induced by erastin and APAP was abrogated by bardoxolone methyl (BM) with less generation of reactive oxygen species and malondialdehyde.
Finally, we report that NRF2 protein expression in a NSCLC cohort exceeds the typical incidence of combined NRF2, KEAP1, and CUL3 mutations, and that NRF2 expression in this cohort is correlated with PIDD levels.
Here we show that Nrf2-mediated NSCLC cell proliferation is dually regulated by epidermal growth factor receptor (EGFR) signaling and an Nrf2 repressor protein Keap1 (Kelch-like ECH-associated protein-1).
Here we show that the activity of this pathway is highly heterogeneous and is regulated by NRF2, a transcription factor frequently deregulated in NSCLC.
In non-small-cell lung cancer (NSCLC) cell lines and NSCLC patients, Keap1 is often present as a biallelic mutant that results in constitutive activation of Nrf2 function, which contributes to cytoprotection against oxidative stress and xenobiotics.
In non-small cell lung cancer (NSCLC) cells and xenografts, MKP-1 knockdown triggered the down-regulation of the metabolic enzymes and cytoprotective proteins, which are the target genes of Nrf2.
In addition, we found a statistically significant correlation between the presence of Keap1/Nrf2 mutations and increased MRP3 messenger RNA levels in our NSCLC patient samples.
In the present study a traditional Chinese medicine, triptolide, was identified that markedly inhibited expression and transcriptional activity of Nrf2 in various cancer cells, including NSCLC and liver cancer cells.
In this study, the increased copy number of the NRF2 gene was analyzed by real-time polymerase chain reaction (real-time-PCR) amplifications in 90 surgically-treated non-small cell lung cancer (NSCLC) cases.
In this study, we discovered that overexpression of antioxidant-responsive element (ARE)-containing Nrf2 target genes by increased transactivation of Nrf2 occurred because of an acquired Keap1 mutation in the gefitinib-resistant (GR) NSCLC cell line we established.
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.