Cancer genome sequencing studies have identified somatic mutations in the KEAP1/NRF2 pathway. In an effort to identify novel NRF2 small molecule inhibitor(s), we have screened a natural compound library comprising 1,330 chemicals in A549-ARE-GFP-luciferase cells and identified that narciclasine significantly inhibits NRF2-dependent luciferase activity. Narciclasine suppressed the expression of NRF2 and NRF2 target genes, caused significant oxidative stress, and sensitized cisplatin-mediated apoptosis in A549 cells. In addition, we have observed that WD Repeat Domain 43 (WDR43) serves as a direct target of narciclasine for the inhibition of NRF2 as narciclasine binds to recombinant WDR43 and silencing attenuated the inhibition of NRF2 by narciclasine in A549 cells. Finally, we observed that administration of narciclasine significantly decreased the growth of A549 xenografts. Together, our results demonstrate that the inhibition of NRF2 by narciclasine is mediated by WDR43 and future studies are necessary to elucidate the exact mechanism how WDR43 mediates the inhibition of NRF2 by narciclasine.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1080/10715762.2025.2451679 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Polo-like kinase 2 ameliorates lipopolysaccharide-induced cardiac injury by blocking cardiomyocyte ferroptosis.
Am J Hypertens
January 2025
Department of Cardiology, The Affiliated Hospital of Xuzhou Medical University; Xuzhou 221004, China.
Background: Polo-like kinase 2 (PLK2) is associated with cardiac fibrosis in patients with atrial fibrillation. However, the role of PLK2 in sepsis-induced cardiac injury has not been fully elucidated. We hypothesize that PLK2 may participate in the progression of sepsis-induced cardiac injury.
View Article and Find Full Text PDFAdhesive and injectable hydrogel microspheres for NRF2-mediated periodontal bone regeneration.
Int J Oral Sci
January 2025
Department of Geriatric Dentistry, Peking University School and Hospital of Stomatology & National Center of Stomatology & National Clinical Research Center for Oral Diseases & National Engineering Laboratory for Digital and Material Technology of Stomatology & Beijing Key Laboratory of Digital Stomatology & Research Center of Engineering and Technology for Computerized Dentistry Ministry of Health & NMPA Key Laboratory for Dental Materials, Beijing, China.
Regenerating periodontal bone defect surrounding periodontal tissue is crucial for orthodontic or dental implant treatment. The declined osteogenic ability of periodontal ligament stem cells (PDLSCs) induced by inflammation stimulus contributes to reduced capacity to regenerate periodontal bone, which brings about a huge challenge for treating periodontitis. Here, inspired by the adhesive property of mussels, we have created adhesive and mineralized hydrogel microspheres loaded with traditional compound cordycepin (MMS-CY).
View Article and Find Full Text PDFEnzyme-assisted Rosa davurica mitigates UV-induced skin photodamage by modulating apoptosis through Nrf2/ARE and MAPK/NF-κB pathways.
J Photochem Photobiol B
January 2025
Graduate School of Biotechnology, Kyung Hee University, 1732 Deogyeong-daero, Giheung, Yongin 17104, Republic of Korea. Electronic address:
Exposure to UV irradiation results in abnormal, extensive apoptosis of skin cells. This excessive cell death can promote inflammation and alter the microenvironment, increasing the risk of skin cancer. Despite extensive research, few materials are effective at simultaneously protecting against both UVA and UVB irradiation.
View Article and Find Full Text PDFSQSTM1/p62 predicts prognosis and upregulates the transcription of CCND1 to promote proliferation in mantle cell lymphoma.
Protoplasma
January 2025
Department of Hematology, Fujian Institute of Hematology, Fujian Provincial Key Laboratory on Hematology, Fujian Medical University Union Hospital, Fuzhou, 350001, China.
Mantle cell lymphoma (MCL) is a rare, highly invasive non-Hodgkin's lymphoma. The main pathogenesis of MCL is associated with the formation of the IgH/CCND1 fusion gene and nuclear overexpression of cyclin D1, which accelerates the cell cycle, leading to tumorigenesis. The prognosis with current standard chemotherapy is still unsatisfactory.
View Article and Find Full Text PDFIdentification of narciclasine as a novel NRF2 inhibitor.
Free Radic Res
January 2025
College of Pharmacy and Integrated Research Institute for Drug Development, Dongguk University, 32 Dongguk-ro, Goyang, Gyeonggi-do 10326, Korea.
Cancer genome sequencing studies have identified somatic mutations in the KEAP1/NRF2 pathway. In an effort to identify novel NRF2 small molecule inhibitor(s), we have screened a natural compound library comprising 1,330 chemicals in A549-ARE-GFP-luciferase cells and identified that narciclasine significantly inhibits NRF2-dependent luciferase activity. Narciclasine suppressed the expression of NRF2 and NRF2 target genes, caused significant oxidative stress, and sensitized cisplatin-mediated apoptosis in A549 cells.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!