ArticleFree radical biology & medicine2013
Nrf2-induced antiapoptotic Bcl-xL protein enhances cell survival and drug resistance.
Article in Free radical biology & medicine, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 111 papers.
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Who cites it
111 citing papers in PubMed, 218 citations in OpenAlex.
- RTA‑408 induces p38‑dependent apoptosis and suppresses cell viability in hepatocellular carcinoma cells.Hepatic oncology · 2026Article
- Ancestral protein reconstruction reveals the mechanism of substrate specificity in FN3K-mediated deglycation.Communications biology · 2026Article
- P62 in colorectal cancer: from inflammation suppression to cancer promotion.Frontiers in immunology · 2026Review
- NRF2-SOX4 complex regulates PSPH in hepatocellular carcinoma and modulates M2 macrophage differentiation.Cancer gene therapy · 2025Article
- Radioprotective Efficacy of Jujube Aqueous Extract and Arbutin: Synergistic Antioxidant and Anti-Apoptotic Mechanisms in Radiation Injury.Food science & nutrition · 2025Article
- Ancestral protein reconstruction reveals the mechanism of substrate specificity in FN3K-mediated deglycation.Research square · 2025Article
- Endoplasmic Reticulum Stress in Cancer.MedComm · 2025Review
- Dimethyl fumarate abrogates hepatocellular carcinoma growth by inhibiting Nrf2/Bcl-xL axis and enhances sorafenib's efficacy.Scientific reports · 2025Article
- A Comparative Study of N-Acetyl Cysteine, Rosuvastatin, and Vitamin E in the Management of Patients with Non-Alcoholic Steatohepatitis: A Randomized Controlled Trial.Pharmaceuticals (Basel, Switzerland) · 2025Article
- The impact of oxidative stress and the NRF2-KEAP1-ARE signaling pathway on anticancer drug resistance.Oncology research · 2025Review
- Dual role of Nrf2 signaling in hepatocellular carcinoma: promoting development, immune evasion, and therapeutic challenges.Frontiers in immunology · 2024Review
- Nrf2-Mediated Antioxidant Response and Drug Efflux Transporters Upregulation as Possible Mechanisms of Resistance in Photodynamic Therapy of Cancers.OncoTargets and therapy · 2024Review
- Regulation of Nrf2/Keap1 signaling pathway in cancer drug resistance by galectin-1: cellular and molecular implications.Cancer drug resistance (Alhambra, Calif.) · 2024Review
- Article
- Camptothecin Sensitizes Hepatocellular Carcinoma Cells to Sorafenib- Induced Ferroptosis Via Suppression of Nrf2.Inflammation · 2023Article
- Advances in Understanding the Role of NRF2 in Liver Pathophysiology and Its Relationship with Hepatic-Specific Cyclooxygenase-2 Expression.Antioxidants (Basel, Switzerland) · 2023Review
- Nrf2: a dark horse in doxorubicin-induced cardiotoxicity.Cell death discovery · 2023Review
- An Adverse Outcome Pathway Network for Chemically Induced Oxidative Stress Leading to (Non)genotoxic Carcinogenesis.Chemical research in toxicology · 2023Review
- Fluid shear stress enhances proliferation of breast cancer cells via downregulation of the c-subunit of the FBiochemical and biophysical research communications · 2022Article
- XAF1 drives apoptotic switch of endoplasmic reticulum stress response through destabilization of GRP78 and CHIP.Cell death & disease · 2022Article
51 more citing papers are in PubMed but not listed here.
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2 authors at 1 institution in 1 country.
Funding
Abstract
Nuclear transcription factor Nrf2 binds with the antioxidant-response element (ARE) in the promoter regions of cytoprotective genes, leading to their increased expression and cellular protection. In this study, we investigated the role of Nrf2 in the regulation of antiapoptotic Bcl-xL protein and its effect on cellular apoptosis. Treatment of mouse Hepa-1 cells with the antioxidant tert-butylhydroquinone led to the induction of Bcl-xL gene expression. Promoter mutagenesis, transfection, and chromatin immunoprecipitation assays identified an ARE between nucleotides -608 and -600 in the forward strand of the proximal Bcl-xL promoter that bound to Nrf2 and led to increased Bcl-xL gene expression. In addition, short interfering RNA (siRNA) inhibition and overexpression of Nrf2 led to a respective decrease and increase in Bcl-xL gene expression. These results implicated Nrf2 in the regulation of expression and induction of Bcl-xL protein. Nrf2-mediated expression of Bcl-xL protein downregulated Bax and decreased caspase 3/7 activity. SiRNA inhibition of both Nrf2 and Bcl-xL increased the susceptibility of cancer cells to etoposide-mediated cell death and reduced cell survival. Moreover, dysfunctional/mutant INrf2 (inhibitor of Nrf2) in human lung cancer cells failed to degrade Nrf2, resulting in increased Bcl-xL levels and increased cell survival. These data provide the first evidence of Nrf2 in the control of Bcl-xL expression and apoptotic cell death with implications for antioxidant protection, survival of cancer cells, and drug resistance.
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