ArticleCancer research2013
Targeting truncated retinoid X receptor-α by CF31 induces TNF-α-dependent apoptosis.
Article in Cancer research, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 40 citations in OpenAlex.
- Article
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- DockStream: a docking wrapper to enhance de novo molecular design.Journal of cheminformatics · 2021Article
- Chemopreventive Effect ofMolecules (Basel, Switzerland) · 2021Article
- Synthesis and biological evaluation of (3/4-(pyrimidin-2-ylamino)benzoyl)-based hydrazine-1-carboxamide/carbothioamide derivatives as novel RXRα antagonists.Journal of enzyme inhibition and medicinal chemistry · 2020Article
- Discovery of atorvastatin as a tetramer stabilizer of nuclear receptor RXRα through structure-based virtual screening.Bioorganic chemistry · 2019Article
- Oncogenic potential of truncated RXRα during colitis-associated colorectal tumorigenesis by promoting IL-6-STAT3 signaling.Nature communications · 2019Article
- Steroids from the Deep-Sea-Derived FungusMarine drugs · 2019Article
- Retinoid X Receptor Antagonists.International journal of molecular sciences · 2018Review
- A 16-gene expression signature to distinguish stage I from stage II lung squamous carcinoma.International journal of molecular medicine · 2018Article
- Overview of the structure-based non-genomic effects of the nuclear receptor RXRα.Cellular & molecular biology letters · 2018Review
- Modulation of nongenomic activation of PI3K signalling by tetramerization of N-terminally-cleaved RXRα.Nature communications · 2017Article
- Targeting to the non-genomic activity of retinoic acid receptor-gamma by acacetin in hepatocellular carcinoma.Scientific reports · 2017Article
- TNF-α -308 A allele is associated with an increased risk of distant metastasis in rectal cancer patients from Southwestern China.PloS one · 2017Article
- α-Mangostin, a Natural Agent, Enhances the Response of NRAS Mutant Melanoma to Retinoic Acid.Medical science monitor : international medical journal of experimental and clinical research · 2016Article
- Targeting truncated RXRα for cancer therapy.Acta biochimica et biophysica Sinica · 2016Review
- Inhibition of Cell Proliferation in an NRAS Mutant Melanoma Cell Line by Combining Sorafenib and α-Mangostin.PloS one · 2016Article
- NSC-640358 acts as RXRα ligand to promote TNFα-mediated apoptosis of cancer cell.Protein & cell · 2015Article
- Nitrostyrene Derivatives Act as RXRα Ligands to Inhibit TNFα Activation of NF-κB.Cancer research · 2015Article
- Regulation of the nongenomic actions of retinoid X receptor-α by targeting the coregulator-binding sites.Acta pharmacologica Sinica · 2015Review
Corrections and comments
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Authors and funding
15 authors at 3 institutions in 2 countries.
Funding
Abstract
A truncated version of retinoid X receptor-α, tRXR-α, promotes cancer cell survival by activating the phosphoinositide 3-kinase (PI3K)/AKT pathway. However, targeting the tRXR-α-mediated survival pathway for cancer treatment remains to be explored. We report here our identification of a new natural product molecule, CF31, a xanthone isolated from Cratoxylum formosum ssp. pruniflorum, and the biologic evaluation of its regulation of the tRXR-α-mediated PI3K/AKT pathway. CF31 binds RXR-α and its binding results in inhibition of RXR-α transactivation. Through RXR-α mutational analysis and computational studies, we show that Arg316 of RXR-α, known to form salt bridges with certain RXR-α ligands, such as 9-cis-retinoic acid (9-cis-RA), is not required for the antagonist effect of CF31, showing a distinct binding mode. Evaluation of several CF31 analogs suggests that the antagonist effect is mainly attributed to an interference with Leu451 of helix H12 in RXR-α. CF31 is a potent inhibitor of AKT activation in various cancer cell lines. When combined with TNF-α, it suppresses TNF-α activation of AKT by inhibiting TNF-α-induced tRXR-α interaction with the p85α regulatory subunit of PI3K. CF31 inhibition of TNF-α activation of AKT also results in TNF-α-dependent activation of caspase-8 and apoptosis. Together, our results show that CF31 is an effective converter of TNF-α signaling from survival to death by targeting tRXR-α in a unique mode and suggest that identification of a natural product that targets an RXR-mediated cell survival pathway that regulates PI3K/AKT may offer a new therapeutic strategy to kill cancer cells.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.