ArticleOncogene2008
The proapoptotic effects of sulindac, sulindac sulfone and indomethacin are mediated by nucleolar translocation of the RelA(p65) subunit of NF-kappaB.
Article in Oncogene, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 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
29 citing papers in PubMed, 53 citations in OpenAlex.
- Article
- The effect of sulindac on redox homeostasis and apoptosis-related proteins in melanotic and amelanotic cells.Pharmacological reports : PR · 2023Article
- Non-steroidal anti-inflammatory drugs and biomarkers: A new paradigm in colorectal cancer.Frontiers in medicine · 2023Review
- The Effect of Low Doses of Acetylsalicylic Acid on the Occurrence of Rectal Aberrant Crypt Foci.Medicina (Kaunas, Lithuania) · 2022Article
- The NF-κB Nucleolar Stress Response Pathway.Biomedicines · 2021Review
- PSMB4 inhibits cardiomyocyte apoptosis via activating NF-κB signaling pathway during myocardial ischemia/reperfusion injury.Journal of molecular histology · 2021Article
- Feedback loop in miR-449b-3p/ADAM17/NF-κB promotes metastasis in nasopharyngeal carcinoma.Cancer medicine · 2019Article
- Review
- Targeting IKKβ in Cancer: Challenges and Opportunities for the Therapeutic Utilisation of IKKβ Inhibitors.Cells · 2018Review
- Cadherin 6 is activated by Epstein-Barr virus LMP1 to mediate EMT and metastasis as an interplay node of multiple pathways in nasopharyngeal carcinoma.Oncogenesis · 2017Article
- Aspirin Prevention of Colorectal Cancer: Focus on NF-κB Signalling and the Nucleolus.Biomedicines · 2017Review
- Ketogal: A Derivative Ketorolac Molecule with Minor Ulcerogenic and Renal Toxicity.Frontiers in pharmacology · 2017Article
- New use for an old drug: COX-independent anti-inflammatory effects of sulindac in models of cystic fibrosis.British journal of pharmacology · 2016Article
- Sulindac, a non-steroidal anti-inflammatory drug, mediates breast cancer inhibition as an immune modulator.Scientific reports · 2016Article
- p300-mediated acetylation of COMMD1 regulates its stability, and the ubiquitylation and nucleolar translocation of the RelA NF-κB subunit.Journal of cell science · 2014Article
- [Interaction of anesthetics and analgesics with tumor cells].Der Anaesthesist · 2014Review
- Molecular pathways: adipose inflammation as a mediator of obesity-associated cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2013Article
- Sulindac activates NF-κB signaling in colon cancer cells.Cell communication and signaling : CCS · 2013Article
- Mechanisms of action of non-steroidal anti-inflammatory drugs (NSAIDs) and mesalazine in the chemoprevention of colorectal cancer.International journal of molecular sciences · 2013Review
- Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 3 institutions in 1 country.
Funding
Abstract
Understanding the mechanisms that underlie the antitumour activity of non-steroidal anti-inflammatory drugs (NSAIDs) against colorectal cancer will allow the development of more effective and specific chemopreventative agents. Modulation of the NF-kappaB pathway has been implicated as a key effector of the antitumour effect of aspirin, but the effects of non-aspirin NSAIDs on this pathway have yet to be fully defined. Here, we demonstrate that sulindac, sulindac sulfone and indomethacin activate the NF-kappaB pathway in colorectal cancer cells, as determined by western blot analysis of cytoplasmic levels of IkappaBalpha and immunocytochemical analysis of nuclear NF-kappaB/RelA. Furthermore, we show that all of these NSAIDs induce nucleolar translocation of the RelA subunit of NF-kappaB. Using RelA deleted for the previously described nucleolar localization signal, we demonstrate that this response is causally involved in the apoptotic effects of these agents. Finally, we demonstrate that NSAID-mediated nucleolar translocation of RelA is associated with downregulation of NF-kappaB-driven transcription and of the NF-kappaB target gene, ICAM-1. These data identify nucleolar translocation of RelA and the associated repression of the NF-kappaB-driven transcription as a central molecular mechanism of NSAID-mediated growth inhibition and apoptosis. As well as providing new understanding of the molecular determinants of RelA function, these findings also have relevance to the development of novel chemotherapeutic and chemopreventative agents.
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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.