Involvement of NRF2 in Breast Cancer and Possible Therapeutical Role of Polyphenols and Melatonin

Abstract

Oxidative stress is defined as a disturbance in the prooxidant/antioxidant balance in favor of the former and a loss of control over redox signaling processes, leading to potential biomolecular damage. It is involved in the etiology of many diseases, varying from diabetes to neurodegenerative diseases and cancer. Nuclear factor erythroid 2-related factor 2 (NRF2) is a transcription factor and reported as one of the most important oxidative stress regulators. Due to its regulatory role in the expression of numerous cytoprotective genes involved in the antioxidant and anti-inflammatory responses, the modulation of NRF2 seems to be a promising approach in the prevention and treatment of cancer. Breast cancer is the prevalent type of tumor in women and is the leading cause of death among female cancers. Oxidative stress-related mechanisms are known to be involved in breast cancer, and therefore, NRF2 is considered to be beneficial in its prevention. However, its overactivation may lead to a negative clinical impact on breast cancer therapy by causing chemoresistance. Some known “oxidative stress modulators”, such as melatonin and polyphenols, are suggested to play an important role in the prevention and treatment of cancer, where the activation of NRF2 is reported as a possible underlying mechanism. In the present review, the potential involvement of oxidative stress and NRF2 in breast cancer will be reviewed, and the role of the NRF2 modulators—namely, polyphenols and melatonin—in the treatment of breast cancer will be discussed.

Neobavaisoflavone May Modulate the Activity of Topoisomerase Inhibitors towards U-87 MG Cells: An In Vitro Study

“…Although these compounds are characterized by their anti-oxidant properties, depending on the conditions, they are able to inhibit anti-oxidant defense system of the cell [45]. This might be due to the modulation of transcriptional factors involved in GSH recycling, e.g., nuclear factor erythroid 2-related factor 2 (Nrf2), as polyphenols have been proved to act in this manner [46,47]. Herein, we report for the first time that NBIF triggers GSH depletion in GB cells (Figure 4A,B).…”

Understanding the Emerging Link Between Circadian Rhythm, Nrf2 Pathway, and Breast Cancer to Overcome Drug Resistance

“…Stress-related DNA adduct formation and aggregation as a result of incomplete DNA repair is an established reality as oxidative stress is elevated in cells. Antioxidant enzymes that sustain redox equilibrium in our body include peroxiredoxin (Prdx), superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) ( Barnes et al, 2018 ; Tascioglu Aliyev et al, 2021 ). Nrf2 is a transcription factor that belongs to the Cap “n” Collar (CNC) family and is encoded by the NFE2L2 gene ( Moi et al, 1994 ).…”

“…Nrf2 is a transcription factor that belongs to the Cap “n” Collar (CNC) family and is encoded by the NFE2L2 gene ( Moi et al, 1994 ). Its expression controls the expression of many cytoprotective genes implicated in antioxidant and anti-inflammatory responses ( Tascioglu Aliyev et al, 2021 ).…”

New Advances on Pathophysiology of Diabetes Neuropathy and Pain Management: Potential Role of Melatonin and DPP-4 Inhibitors

“…The modulative effects of melatonin on inflammation and autophagy are one of the significant mechanisms through which melatonin alleviates DNP ( Jangra, Datusalia, Khandwe, & Sharma, 2013 ). Melatonin promotes the expression of nuclear factor erythroid-2 related factor 2 (Nrf2), which consequently activates phase II antioxidant enzymes such as heme oxygenase-1 (HO-1) and offers protection from oxidative damage ( Ahmadi & Ashrafizadeh, 2020 ; Aliyev, Panieri, Stepanic, Gurer-Orhan, & Saso, 2021 ). Melatonin is also known to stimulate PTEN-induced putative kinase 1 (PINK1 expression) via an MT2/Akt/NF-κB pathway.…”