ArticleMolecular oncology2015
Natural product (-)-gossypol inhibits colon cancer cell growth by targeting RNA-binding protein Musashi-1.
Article in Molecular oncology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 73 papers.
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Who cites it
73 citing papers in PubMed, 121 citations in OpenAlex.
- Plant-Derived Bioactive Compounds and Their Therapeutic Potential in Cancer.International journal of molecular sciences · 2026Review
- Targeting RNA binding proteins with small-molecule inhibitors: Advances, challenges, and therapeutic opportunities.Acta pharmaceutica Sinica. B · 2026Review
- The intricate dance of RNA-binding proteins: unveiling the mechanisms behind male infertility.Human reproduction update · 2026Review
- The role of RNA binding proteins in cancer biology: A focus on FMRP.Genes & diseases · 2025Review
- Energy metabolism in health and diseases.Signal transduction and targeted therapy · 2025Review
- Biopolymeric nanocarriers in cancer therapy: unleashing the potency of bioactive anticancer compounds for enhancing drug delivery.RSC advances · 2024Review
- Review
- 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
- Rationally designed stapled peptides allosterically inhibit PTBP1-RNA-binding.Chemical science · 2023Article
- Surmounting Cancer Drug Resistance: New Perspective on RNA-Binding Proteins.Pharmaceuticals (Basel, Switzerland) · 2023Review
- MSI2 promotes translation of multiple IRES-containing oncogenes and virus to induce self-renewal of tumor initiating stem-like cells.Cell death discovery · 2023Article
- Novel roles of RNA-binding proteins in drug resistance of breast cancer: from molecular biology to targeting therapeutics.Cell death discovery · 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.bioRxiv : the preprint server for biology · 2023Article
- Rationally designed inhibitors of the Musashi protein-RNA interaction by hotspot mimicry.Research square · 2023Article
- Using the structural diversity of RNA: protein interfaces to selectively target RNA with small molecules in cells: methods and perspectives.Frontiers in molecular biosciences · 2023Review
- RNA binding proteins (RBPs) and their role in DNA damage and radiation response in cancer.Advanced drug delivery reviews · 2022Review
- Gossypol and Its Natural Derivatives: Multitargeted Phytochemicals as Potential Drug Candidates for Oncologic Diseases.Pharmaceutics · 2022Review
- Identification ofMolecules (Basel, Switzerland) · 2022Article
13 more citing papers are in PubMed but not listed here.
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Authors and funding
20 authors at 4 institutions in 2 countries.
Funding
Abstract
Musashi-1 (MSI1) is an RNA-binding protein that acts as a translation activator or repressor of target mRNAs. The best-characterized MSI1 target is Numb mRNA, whose encoded protein negatively regulates Notch signaling. Additional MSI1 targets include the mRNAs for the tumor suppressor protein APC that regulates Wnt signaling and the cyclin-dependent kinase inhibitor P21(WAF-1). We hypothesized that increased expression of NUMB, P21 and APC, through inhibition of MSI1 RNA-binding activity might be an effective way to simultaneously downregulate Wnt and Notch signaling, thus blocking the growth of a broad range of cancer cells. We used a fluorescence polarization assay to screen for small molecules that disrupt the binding of MSI1 to its consensus RNA binding site. One of the top hits was (-)-gossypol (Ki = 476 ± 273 nM), a natural product from cottonseed, known to have potent anti-tumor activity and which has recently completed Phase IIb clinical trials for prostate cancer. Surface plasmon resonance and nuclear magnetic resonance studies demonstrate a direct interaction of (-)-gossypol with the RNA binding pocket of MSI1. We further showed that (-)-gossypol reduces Notch/Wnt signaling in several colon cancer cell lines having high levels of MSI1, with reduced SURVIVIN expression and increased apoptosis/autophagy. Finally, we showed that orally administered (-)-gossypol inhibits colon cancer growth in a mouse xenograft model. Our study identifies (-)-gossypol as a potential small molecule inhibitor of MSI1-RNA interaction, and suggests that inhibition of MSI1's RNA binding activity may be an effective anti-cancer strategy.
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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.