ArticleBMC cancer2018
Natural product derivative Gossypolone inhibits Musashi family of RNA-binding proteins.
Article in BMC cancer, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
22 citing papers in PubMed, 1 synthesis or guideline pooled it, 42 citations in OpenAlex.
- Prognostic value of Musashi 2 (MSI2) in cancer patients: A systematic review and meta-analysis.Frontiers in oncology · 2022Pooled it
- Review
- RNA-binding proteins in the mouse lens: Functional classifications, expression profiling, and interaction studies of Carhsp1 with crystallin mRNAs.Developmental biology · 2026Article
- In Vitro and In Vivo Evaluation of Lactoferrin-Modified Liposomal Etomidate with Enhanced Brain-Targeting Effect for General Anesthesia.Pharmaceutics · 2024Article
- Small-molecule Ro-08-2750 interacts with many RNA-binding proteins and elicits MUSASHI2-independent phenotypes.RNA (New York, N.Y.) · 2023Article
- The Musashi RNA-binding proteins in female cancers: insights on molecular mechanisms and therapeutic relevance.Biomarker research · 2023Review
- (-)- Gossypol Inhibition of Musashi-Mediated Forgetting Improves Memory and Age-Dependent Memory Decline in Caenorhabditis elegans.Molecular neurobiology · 2023Article
- Rationally designed inhibitors of the Musashi protein-RNA interaction by hotspot mimicry.Research square · 2023Article
- Rationally designed inhibitors of the Musashi protein-RNA interaction by hotspot mimicry.bioRxiv : the preprint server for biology · 2023Article
- [Advances in research of Musashi2 in solid tumors].Nan fang yi ke da xue xue bao = Journal of Southern Medical University · 2022Review
- RNA-binding proteins and their role in kidney disease.Nature reviews. Nephrology · 2022Review
- Inhibition and potential treatment of colorectal cancer by natural compoundsFrontiers in oncology · 2022Review
- Mechanism of RNA recognition by a Musashi RNA-binding protein.Current research in structural biology · 2022Review
- Cyclic RGD-Decorated Liposomal Gossypol AT-101 Targeting for Enhanced Antitumor Effect.International journal of nanomedicine · 2022Article
- Musashi-1-A Stemness RBP for Cancer Therapy?Biology · 2021Review
- Article
- Small Molecule Palmatine Targeting Musashi-2 in Colorectal Cancer.Frontiers in pharmacology · 2021Article
- Potential Role of Musashi-2 RNA-Binding Protein in Cancer EMT.OncoTargets and therapy · 2021Review
- Identification and Validation of anCancers · 2020Article
- RNA-Targeted Therapies and High-Throughput Screening Methods.International journal of molecular sciences · 2020Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
17 authors at 4 institutions in 2 countries.
Funding
Abstract
backgroundThe Musashi (MSI) family of RNA-binding proteins is best known for the role in post-transcriptional regulation of target mRNAs. Elevated MSI1 levels in a variety of human cancer are associated with up-regulation of Notch/Wnt signaling. MSI1 binds to and negatively regulates translation of Numb and APC (adenomatous polyposis coli), negative regulators of Notch and Wnt signaling respectively.
methodsPreviously, we have shown that the natural product (-)-gossypol as the first known small molecule inhibitor of MSI1 that down-regulates Notch/Wnt signaling and inhibits tumor xenograft growth in vivo. Using a fluorescence polarization (FP) competition assay, we identified gossypolone (Gn) with a > 20-fold increase in Ki value compared to (-)-gossypol. We validated Gn binding to MSI1 using surface plasmon resonance, nuclear magnetic resonance, and cellular thermal shift assay, and tested the effects of Gn on colon cancer cells and colon cancer DLD-1 xenografts in nude mice.
resultsIn colon cancer cells, Gn reduced Notch/Wnt signaling and induced apoptosis. Compared to (-)-gossypol, the same concentration of Gn is less active in all the cell assays tested. To increase Gn bioavailability, we used PEGylated liposomes in our in vivo studies. Gn-lip via tail vein injection inhibited the growth of human colon cancer DLD-1 xenografts in nude mice, as compared to the untreated control (P < 0.01, n = 10).
conclusionOur data suggest that PEGylation improved the bioavailability of Gn as well as achieved tumor-targeted delivery and controlled release of Gn, which enhanced its overall biocompatibility and drug efficacy in vivo. This provides proof of concept for the development of Gn-lip as a molecular therapy for colon cancer with MSI1/MSI2 overexpression.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.