Background: In previous study, n-butylidenephthalide (BP), a natural compound from Angelica sinensis, has anti-glioblastoma multiform (GBM) cell effects. In this study, we modified BP structure to increase anti-GBM cell effects. The anti-GBM cell effects of one derivative of BP, (Z)-N-(2-(dimethylamino)ethyl)-2-(3-((3-oxoisobenzofuran-1(3H)-ylidene)methyl)phenoxy)acetamide (PCH4) were tested in vitro and in vivo.
Methods: MTT assay and PI/Annexin V assay were performed to evaluate the anti-GBM effects of PCH4. The Nur77 expression and translocation were assayed by RT-PCR and Western blot. The Nur77 siRNA was used to downregulate the Nur77 expression. The JNK inhibitor (SP600125) was used to block the JNK pathway.
Results: The anti-GBM effect of PCH4 is four times more than BP. The IC(50) of PCH4 on DBTRG-05MG cells was 50 µg/ml. Nur77 expression and translocation from the nucleus to the cytoplasm were important in PCH4-induced apoptosis. Furthermore, the downregulation of PCH4-induced Nur77 expression by Nur77 siRNA reduced PCH4-induced apoptosis. In addition, PCH4-induced apoptosis was associated with the JNK pathway. The JNK inhibitor, SP600125, inhibited Nur77 mRNA expression and reduced PCH4-induced apoptosis.
Conclusions: In conclusion, PCH4, a derivative of BP, induced Nur77-mediated apoptosis via the JNK pathway and this mechanism, which is different from that of BP, may explain the increase in the anti-tumor effects on GBM.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1002/jso.21809 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Design, synthesis, and biological evaluation of N-(2-(adamantan-1-yl)-1H-indol-5-yl)-N-(substituent)-1,2-dicarboxamides as anticancer agents targeting Nur77-mediated endoplasmic reticulum stress.
Bioorg Chem
December 2024
State Key Laboratory of Cellular Stress Biology, Fujian Provincial Key Laboratory of Innovative Drug Target Research, School of Pharmaceutical Sciences, Faculty of Medicine and Life Sciences, Xiamen University, Xiamen 361102, China. Electronic address:
Targeting endoplasmic reticulum (ER) stress-induced apoptosis has attracted considerable research interest in anti-cancer drug development. Nur77 is a potential therapeutic target in many cancers and several Nur77 modulators have recently been identified as effective anticancer agents by activating ER stress. As an ongoing work, this study reports a new series of novel N-(2-(adamantan-1-yl)-1H-indol-5-yl)-N-(substituent)-1,2-dicarboxamides as potent Nur77 modulators that cause ER stress-induced apoptosis.
View Article and Find Full Text PDFLentinan inhibits melanoma development by regulating the AKT/Nur77/Bcl-2 signaling axis.
J Cancer
January 2025
Engineering Technological Center of Mushroom Industry, Minnan Normal University, Zhangzhou, Fujian 363000, People's Republic of China.
Article Synopsis
- Lentinan (LNT), a natural product, shows strong anti-tumor effects against melanoma and could be a potential treatment option.
- Research utilized a mouse model and various assays to demonstrate that LNT significantly inhibits melanoma cell growth and proliferation.
- The study found that LNT induces apoptosis in melanoma cells by regulating the Nur77/Bcl-2 pathway and influences cell signaling through the AKT pathway.
Nuclear receptor subfamily 4 group a member 1 eases angiotensin II-arose oxidative stress in vascular smooth muscle cell by boosting nucleotide-binding oligomerization domain-like receptor family caspase recruitment domain containing 3 transcription.
Cytojournal
November 2024
The Third School of Clinical Medicine, Southern Medical University, Guangzhou, Guangdong, China.
Objective: Hypertension significantly contributes to morbidity and mortality. Nuclear receptor subfamily 4 group a member 1 (Nur77) participates in regulating oxidative stress, but the mechanism in hypertension remains unclear. This study aimed to explore the function of Nur77 in oxidative stress induced by Angiotensin II (Ang II) in vascular smooth muscle cells (VSMCs) in hypertension.
View Article and Find Full Text PDFExogenous α-Synuclein Induces Oxidative Damage to Dopaminergic Neurons Through p-NMDAR2B/Nur77.
Mol Neurobiol
November 2024
Key Laboratory of Neuromolecular Biology, The First Affiliated Hospital of Henan University of Science and Technology, Luoyang, China.
Alpha-synuclein (α-syn) is a major pathological marker of Parkinson's disease (PD), and its abnormal expression and aggregation lead to dopaminergic neuron degeneration, in which oxidative stress plays an important role. However, the exact molecular mechanism by which α-syn causes PD remains unclear. In this study, exogenous α-syn, also known as α-syn preformed fibrils (α-syn PFFs), was used to construct in vivo and in vitro models of PD.
View Article and Find Full Text PDFCHIP drives proteasomal degradation of NUR77 to alleviate oxidative stress and intrinsic apoptosis in cisplatin-induced nephropathy.
Commun Biol
October 2024
Department of Urology, The Second Xiangya Hospital at Central South University, Changsha, Hunan, 410011, China.
Article Synopsis
- CHIP (Carboxy-terminus of Hsc70-interacting protein) is an E3 ligase that helps regulate protein stability and plays a crucial role in reducing damage from acute kidney injury (AKI), especially related to cisplatin treatment.
- In cisplatin-induced AKI, CHIP levels decrease, leading to increased oxidative stress and cell death in renal proximal tubular cells.
- The study shows that CHIP promotes the degradation of NUR77, a protein that contributes to apoptosis, thus suggesting a protective mechanism against kidney damage caused by cisplatin.
Want 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!