ArticleJournal of experimental & clinical cancer research : CR2016
The 1,4 benzoquinone-featured 5-lipoxygenase inhibitor RF-Id induces apoptotic death through downregulation of IAPs in human glioblastoma cells.
Article in Journal of experimental & clinical cancer research : CR, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 23 citations in OpenAlex.
- Embelin Mitigates the Impact of Perinatal Inflammation on Neuron Development by Inhibiting 5-Lipoxygenase-Mediated Ferroptosis.Phytotherapy research : PTR · 2025Article
- Immune cell infiltration and inflammatory landscape in primary brain tumours.Journal of translational medicine · 2024Article
- A review on potential heterocycles for the treatment of glioblastoma targeting receptor tyrosine kinases.Oncology research · 2024Review
- Regulated cell death in glioma: promising targets for natural small-molecule compounds.Frontiers in oncology · 2024Review
- Formulation and Characterization of Solid Lipid Nanoparticles Loading RF22-c, a Potent and Selective 5-LO Inhibitor, in a Monocrotaline-Induced Model of Pulmonary Hypertension.Frontiers in pharmacology · 2020Article
- Identification of Prognostic Model and Biomarkers for Cancer Stem Cell Characteristics in Glioblastoma by Network Analysis of Multi-Omics Data and Stemness Indices.Frontiers in cell and developmental biology · 2020Article
- A Hydroquinone-Based Derivative Elicits Apoptosis and Autophagy via Activating a ROS-Dependent Unfolded Protein Response in Human Glioblastoma.International journal of molecular sciences · 2019Article
- CBioMed research international · 2019Article
- Phenethyl Isothiocyanate Inhibits In Vivo Growth of Xenograft Tumors of Human Glioblastoma Cells.Molecules (Basel, Switzerland) · 2018Article
- Hydroquinone Exhibits In Vitro and In Vivo Anti-Cancer Activity in Cancer Cells and Mice.International journal of molecular sciences · 2018Article
- XIAP Limits Autophagic Degradation of Sox2 and Is A Therapeutic Target in Nasopharyngeal Carcinoma Stem Cells.Theranostics · 2018Article
- Up-regulation of 5-lipoxygenase by inhibition of cathepsin G enhances TRAIL-induced apoptosis through down-regulation of survivin.Oncotarget · 2017Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundEmbelin is a potent dual inhibitor of 5-lipoxigenase (5-LOX) and microsomal prostaglandin E2 synthase (mPGES)-1 that suppresses proliferation of human glioma cells and induces apoptosis by inhibiting XIAP and NF-κB signaling pathway. Synthetic structural modification yielded the derivative 3-((decahydronaphthalen-6-yl)methyl)-2,5-dihydroxycyclohexa-2,5-diene-1,4-dione (RF-Id), an embelin constrained analogue, with improved efficiency against 5-LOX in human neutrophils and anti-inflammatory activity in vivo. Taking into account that lipoxygenase (LOX) metabolites, from arachidonic acid and linoleic acid, have been implicated in tumor progression, here, we determined whether RF-Id was able to hinder glioblastoma (GBM) cancer cell growth and the related mechanisms.
methodsU87MG and LN229 cells were plated in 96-wells and treated with increasing concentrations of RF-Id. Cell viability was evaluated by MTT assay. The effects of the compounds on cell cycle, apoptosis, oxidative stress and autophagy were assessed by flow cytometry (FACS). The mode of action was confirmed by Taqman apoptosis array and evaluating caspase cascade and NFκB pathway by western blotting technique.
resultsHere, we found that RF-Id induced a stronger inhibition of GBM cell growth than treatment with embelin. Flow cytometry analysis showed that RF-Id induced about 30 % apoptosis and a slight increase of autophagy after 72 h on U87-MG cells. Moreover, the compound induced an increase in the percentage of cells in G2 and S phase that was paralleled by an increase of p21 and p27 expression but no significant changes of the mitochondrial membrane potential; array analysis showed a significant upregulation of CASP8 and a downregulation of IAP family and NFκB genes in cells treated with RF-Id. RF-Id induced a significant cleavage of caspases 8, 9, 3 and 7, blocked c-IAP2/XIAP interaction by inducing XIAP degradation and inhibited NFκB pathway.
conclusionsRF-Id induced a caspase-dependent apoptosis in GBM cells by inhibiting IAP family proteins and NFκB pathway and represents a promising lead compound for designing a new class of anti-cancer drugs with multiple targets.
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