NRF2: New Mechanistic Insights and Therapeutic Perspectives

Kupiec‐Weglinski, Jerzy W.

doi:10.1089/ars.2023.0398

Cited by 4 publications

(1 citation statement)

References 7 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…During ferroptosis, TfR1 and FTH1 are upregulated and downregulated, respectively, suggesting an increase in cellular iron uptake and decrease in the capacity to store iron, leading to the accumulation of more free iron and induction of ferroptosis (Jiang et al., 2020). Various genes are involved in ferroptosis, and Nrf2 is a key transcriptional regulator that participates in the antioxidant stress response (Kupiec‐Weglinski, 2023). When nuclear entry of Nrf2 is blocked, it affects the transcription of antioxidant genes, resulting in weakened cellular antioxidant capacity (Shin et al., 2018).…”

Section: Discussionmentioning

confidence: 99%

Brusatol induces ferroptosis to inhibit hepatocellular carcinoma progression by targeting ATF3

Wan,

Cheng,

Gan

et al. 2024

Chem Biol Drug Des

View full text Add to dashboard Cite

Ferroptosis is a novel form of programmed cell death that is triggered by iron‐dependent lipid peroxidation. Brusatol (BRU), a natural nuclear factor erythroid 2‐related factor 2 inhibitor, exhibits potent anticancer effects in various types of cancer. However, the exact mechanism of BRU in the treatment of hepatocellular carcinoma (HCC) remains unknown. The anticancer effects of BRU in HCC were detected using cell counting kit‐8 and colony formation assays and a xenograft model. RNA sequencing (RNA‐seq) and bioinformatics analyses of HCC cells were utilized to elucidate the mechanism underlying the effects of BRU in HCC. The levels of reactive oxygen species (ROS), glutathione (GSH), malondialdehyde (MDA), and Fe2+ were measured using assay kits. The expression of activating transcription factor 3 (ATF3) was tested using RT‐qPCR, western blotting, and immunofluorescence staining. The role of ATF3 in BRU‐induced ferroptosis was examined using siATF3. BRU significantly inhibited HCC cell proliferation, both in vitro and in vivo. BRU activated the ferroptosis signaling pathway and increased ATF3 expression. Furthermore, ATF3 knockdown impeded BRU‐induced ferroptosis. BRU suppressed HCC growth through ATF3‐mediated ferroptosis, supporting BRU as a promising therapeutic agent for HCC.

show abstract

Section: Discussionmentioning

confidence: 99%

Brusatol induces ferroptosis to inhibit hepatocellular carcinoma progression by targeting ATF3

Wan,

Cheng,

Gan

et al. 2024

Chem Biol Drug Des

View full text Add to dashboard Cite

show abstract

Solasodine Downregulates ABCB1 Overexpression in Multidrug Resistant Cancer Cells Via Inhibiting Nrf2/Keap1 Signaling Pathway

Bharathiraja,

Baskar,

Prasad

2024

J of Cellular Biochemistry

View full text Add to dashboard Cite

Multidrug‐resistant (MDR) cancer cells maintain redox homeostasis to eliminate oxidative stress‐mediated cell death. This study explores the effects of solasodine on regulating P‐glycoprotein (P‐gp) expression through the Nrf2/Keap1 signaling pathway and oxidative stress‐induced sensitization of drug‐resistant cancer cells to chemotherapeutics. Initially, the oxidative stress indicators such as intracellular ROS generation, the levels of 8‐hydroxy‐2‐deoxyguanosine (8‐OHdG) and gamma‐H2AX (γ‐H2AX) in the KBChR‐8‐5 drug‐resistant cells were measured. Additionally, the protein expression levels of Nuclear factor erythroid 2‐related factor 2 (Nrf‐2), Kelch‐like ECH‐associated protein 1 (Keap1), and ATP Binding Cassette Subfamily B Member 1 (ABCB1)/P‐gp were measured at various concentrations of solasodine (1, 5, & 10 µM) through immunofluorescence and western blot analysis. The antioxidant activities in the KBChR‐8‐5 cells were assessed using established protocols. In this investigation, the treatment with solasodine and doxorubicin combination showed a notable increase in intracellular ROS generation in KBChR‐8‐5 cells. Furthermore, this combination treatment led to enhanced nuclear condensation, elevated levels of 8‐OHdG, and increased γ‐H2AX foci formation in the KBChR‐8‐5 cells. Solasodine treatment effectively inhibited the nuclear translocation of Nrf2 and activation of the ABCB1 gene, consequently preventing overexpression of P‐gp in KBChR‐8‐5 cells. Additionally, the combination therapy increased the lipid peroxidation levels while simultaneously reducing the activities of antioxidant enzymes such as superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and the levels of glutathione (GSH). These results demonstrated that solasodine disrupts redox balance, and overcomes drug resistance by downregulating P‐gp via regulating Nrf2/Keap1 signaling pathway in MDR cancer cells.

show abstract

Effects of intermittent exposure to hypobaric hypoxia and cold on skeletal muscle regeneration: Mitochondrial dynamics, protein oxidation and turnover

Sánchez-Nuño,

Santocildes,

Rebull

et al. 2024

Free Radical Biology and Medicine

View full text Add to dashboard Cite

NRF2: New Mechanistic Insights and Therapeutic Perspectives

Cited by 4 publications

References 7 publications

Brusatol induces ferroptosis to inhibit hepatocellular carcinoma progression by targeting ATF3

Brusatol induces ferroptosis to inhibit hepatocellular carcinoma progression by targeting ATF3

Solasodine Downregulates ABCB1 Overexpression in Multidrug Resistant Cancer Cells Via Inhibiting Nrf2/Keap1 Signaling Pathway

Effects of intermittent exposure to hypobaric hypoxia and cold on skeletal muscle regeneration: Mitochondrial dynamics, protein oxidation and turnover

Contact Info

Product

Resources

About