ArticleCancer cell2010
NSAID sulindac and its analog bind RXRalpha and inhibit RXRalpha-dependent AKT signaling.
Article in Cancer cell, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 70 papers.
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
70 citing papers in PubMed, 122 citations in OpenAlex.
- Autophagy: From Molecular Mechanisms to Disease Regulation and Therapeutic Strategies.Current issues in molecular biology · 2026Review
- RXRActa pharmaceutica Sinica. B · 2025Article
- Role of Nuclear Receptors on the Progression of Multiple Sclerosis: A Review.Cellular and molecular neurobiology · 2025Review
- Article
- A Narrative Overview of Retinoid X Receptor Inhibitors in Chronic Disease Management.Current drug research reviews · 2025Review
- Article
- Sulindac (K-80003) with nab-paclitaxel and gemcitabine overcomes drug-resistant pancreatic cancer.Molecular cancer · 2024Article
- Sulindac selectively induces autophagic apoptosis of GABAergic neurons and alters motor behaviour in zebrafish.Nature communications · 2023Article
- Absolute Stereochemistry Determination of Bioactive Marine-Derived Cyclopeptides by Liquid Chromatography Methods: An Update Review (2018-2022).Molecules (Basel, Switzerland) · 2023Review
- K-80003 Inhibition of Macrophage Apoptosis and Necrotic Core Development in Atherosclerotic Vulnerable Plaques.Cardiovascular drugs and therapy · 2022Article
- Atorvastatin favorably modulates a clinical hepatocellular carcinoma risk gene signature.Hepatology communications · 2022Article
- Oncogenic potential of BEST4 in colorectal cancer via activation of PI3K/Akt signaling.Oncogene · 2022Article
- Targeting cancer-related inflammation with non-steroidal anti-inflammatory drugs: Perspectives in pharmacogenomics.Frontiers in pharmacology · 2022Review
- Phase separation of Nur77 mediates celastrol-induced mitophagy by promoting the liquidity of p62/SQSTM1 condensates.Nature communications · 2021Article
- Combination of Sulindac and Bexarotene for Prevention of Intestinal Carcinogenesis in Familial Adenomatous Polyposis.Cancer prevention research (Philadelphia, Pa.) · 2021Article
- The retinoid X receptor α modulator K-80003 suppresses inflammatory and catabolic responses in a rat model of osteoarthritis.Scientific reports · 2021Article
- Article
- Effects of Visceralising Leishmania on the Spleen, Liver, and Bone Marrow: A Pathophysiological Perspective.Microorganisms · 2021Review
- Loss of retinoid X receptor gamma subunit impairs group 1 mGluR mediated electrophysiological responses and group 1 mGluR dependent behaviors.Scientific reports · 2021Article
- Chemoprevention in Barrett's esophagus and esophageal adenocarcinoma.Therapeutic advances in gastroenterology · 2021Review
10 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
24 authors at 4 institutions in 2 countries.
Funding
Abstract
Nonsteroidal anti-inflammatory drugs (NSAIDs) exert their anticancer effects through cyclooxygenase-2 (COX-2)-dependent and independent mechanisms. Here, we report that Sulindac, an NSAID, induces apoptosis by binding to retinoid X receptor-alpha (RXRalpha). We identified an N-terminally truncated RXRalpha (tRXRalpha) in several cancer cell lines and primary tumors, which interacted with the p85alpha subunit of phosphatidylinositol-3-OH kinase (PI3K). Tumor necrosis factor-alpha (TNFalpha) promoted tRXRalpha interaction with the p85alpha, activating PI3K/AKT signaling. When combined with TNFalpha, Sulindac inhibited TNFalpha-induced tRXRalpha/p85alpha interaction, leading to activation of the death receptor-mediated apoptotic pathway. We designed and synthesized a Sulindac analog K-80003, which has increased affinity to RXRalpha but lacks COX inhibitory activity. K-80003 displayed enhanced efficacy in inhibiting tRXRalpha-dependent AKT activation and tRXRalpha tumor growth in animals.
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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.