The effect of NRF2 overexpression in many malignancies is still unclear and recent meta-analysis correlated NRF2 overexpression with poor prognosis in a variety of human cancers.
The mitogen-activated protein kinases (MAPKs) are fundamental in inflammation and cancer control, through the crosstalk between the redox regulated nuclear factor E2-related factor 2 (Nrf2) and nuclear factor-kB (NFκB) gene expression.
It is tempting to speculate that the cancer cell of origin and e-CSCs are closely related entities. e-CSCs possess a hybrid phenotype, sharing key hallmarks of senescence, "stemness" and cancer. e-CSCs are hyper-proliferative and have elevated mitochondrial metabolism, with an NRF2-mediated anti-oxidant response signature, including glutaredoxin (GLRX) and ALDH3A1 over-expression, possibly related to their escape from senescence.
In this review, we emphasize that resveratrol can induce autophagy in the treatment of cancer and accelerates the degradation of p62, and then, the mTOR activation is blocked and Nrf2 activation is suppressed.
Here, we jointly analyzed the Broad-Novartis Cancer Cell Line Encyclopedia (CCLE) and the Cancer Genome Atlas (TCGA) multi-omics data in order to identify cancer types where Nrf2 activation is present.
While Nrf2 activation may counter increasing oxidative stress in aging, its activation in cancer can promote cancer progression and metastasis, and confer resistance to chemotherapy and radiotherapy.
Given the major nephrotoxicity of cisplatin cancer chemotherapy, TMP might be a potential candidate for neoadjuvant chemotherapy due to its antioxidant, anti-inflammatory and anti-apoptotic effects, in addition to its effect on Nrf2, HMGB1/TLR4/NF-κB signaling pathway and PPAR-γ expression.
Intriguingly, constitutive activation of NRF2 promotes cancer development as well as resistance to chemotherapy and radiotherapy, and these malignant phenotypes lead to a poor prognosis in lung cancer patients.
Few studies on the potential undesired effects of flavonoid intake during chemotherapy have been conducted, yet Nrf2 activators could favor cancer cell survival by attenuating chemotherapeutic efficiency.
After further attachment with i-motif DNA/Nrf2 siRNA chimera to simultaneously suppress both cellular antioxidant defense and hyperthermia resistance effects, the final biocompatible CF<sub>5k</sub>-<i>b</i>PEA@siRNA NRs present promising NIR fluorescence imaging ability and 808 nm laser-activated photothermal and photodynamic therapeutic effect in MCF7 cells and tumor-bearing mice, holding great potential for cancer therapy.
In summary, our study reveals a surprising role for the glycation of cellular proteins and implicates FN3K as targetable modulator of NRF2 activity in cancer.
Ultimately, defining and understanding the mechanisms responsible for NRF2 activation in cancer may lead to novel targets for therapeutic intervention.
Finally, although TrxR1-null and TrxR1/Gsr-null livers showed strong Nrf2 activity in noncancerous hepatocytes, there was no correlation between malignancy and Nrf2 expression within tumors across genotypes.