Nuclear factor (erythroid-derived 2)-like-2 factor (NRF-2) is a transcription factor well known to provide an advantage for cancer growth and survival regulating the cellular redox pathway.
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.
Recently, many studies have shown that most of the genes in the Nrf2/Keap1/nuclear factor kappa-B (NF-κB)/phosphotyrosine-independent ligand for the Lck SH2 domain Of 62 KDa (p62) pathway show abnormally high mutational variations in cancer.
Nuclear factor, erythroid 2-like 2 (Nrf2) is a transcription factor that has been gaining attention in the field of pharmacology and especially in the chemoprevention of diseases such as cancer, metabolic and neurodegenerative diseases, etc.
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.
Furthermore, we discuss the role of NRF2 in cancer, neurodegeneration, and diabetes as well as cardiovascular, kidney, and liver disease, with a special emphasis on NRF2-based therapeutics, including those that have made it into clinical trials.
The sesquiterpene-coumarin ether samarcandone provided a suitable framework to replace the apocarotenoid A-C ring system of strigol (<b>1</b>), replicating, after linking to a butenolide moiety, the activity of the natural phytohormone on Nrf2 and also showing potent NF-kB inhibitory activity, overall modulating two critical pathways of inflammation and cancer.
In contrast, at weeks 10 and 16, Nrf2 and its-related anti-oxidant enzymes and NLRP3 inflammasome were highly expressed in M-AOM/DSS group and in F-AOM/DSS group, who developed cancer.
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.
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.
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.
A big number of Nrf2-antioxidant response element activators have been screened for use as chemo-preventive drugs in OS associated diseases like cancer even though activation of Nrf2 happens in a variety of cancers.
Ultimately, defining and understanding the mechanisms responsible for NRF2 activation in cancer may lead to novel targets for therapeutic intervention.
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 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.
Nrf2's role in cancer prevention, diagnosis, prognosis, and therapy is still in its infancy, and the future strategic planning of Nrf2-based oncological approaches should also consider the complex interaction between Nrf2 and its various activators and inhibitors.
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.