ArticleJournal of neuroscience research2013
Sulindac sulfide inhibits sarcoendoplasmic reticulum Ca2+ ATPase, induces endoplasmic reticulum stress response, and exerts toxicity in glioma cells: relevant similarities to and important differences from celecoxib.
Article in Journal of neuroscience research, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 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
18 citing papers in PubMed, 26 citations in OpenAlex.
- Targeting SERCA2 in Anti-Tumor Drug Discovery.Current drug targets · 2025Review
- Endoplasmic Reticulum Stress in Gliomas: Exploiting a Dual-Effect Dysfunction through Chemical Pharmaceutical Compounds and Natural Derivatives for Therapeutical Uses.International journal of molecular sciences · 2024Review
- PIKFYVE inhibitors trigger interleukin-24-dependent cell death of autophagy-dependent melanoma.Molecular oncology · 2024Article
- Targeting cancer-related inflammation with non-steroidal anti-inflammatory drugs: Perspectives in pharmacogenomics.Frontiers in pharmacology · 2022Review
- Endoplasmic Reticulum Calcium Pumps and Tumor Cell Differentiation.International journal of molecular sciences · 2020Review
- ANS Interacts with the CaJournal of fluorescence · 2020Article
- Characterizing Cell Stress and GRP78 in Glioma to Enhance Tumor Treatment.Frontiers in oncology · 2020Review
- Modulating the wnt signaling pathway with small molecules.Protein science : a publication of the Protein Society · 2017Review
- Role of endoplasmic reticulum stress on cisplatin resistance in ovarian carcinoma.Oncology letters · 2017Article
- Celecoxib Inhibits Prion Protein 90-231-Mediated Pro-inflammatory Responses in Microglial Cells.Molecular neurobiology · 2016Article
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- The deadly connection between endoplasmic reticulum, Ca2+, protein synthesis, and the endoplasmic reticulum stress response in malignant glioma cells.Neuro-oncology · 2014Article
- Anti-tumor activity of non-steroidal anti-inflammatory drugs: cyclooxygenase-independent targets.Cancer letters · 2014Review
- Identification of agents that promote endoplasmic reticulum stress using an assay that monitors luciferase secretion.Journal of biomolecular screening · 2014Article
- NSAIDs inhibit tumorigenesis, but how?Clinical cancer research : an official journal of the American Association for Cancer Research · 2014Review
- Anticancer activity and chemoprevention of xenobiotic organosulfurs in preclinical model systems.Oncology discovery · 2013Article
- COX-Independent Mechanisms of Cancer Chemoprevention by Anti-Inflammatory Drugs.Frontiers in oncology · 2013Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Malignant gliomas have low survival expectations regardless of current treatments. Nonsteroidal anti-inflammatory drugs (NSAIDs) prevent cell transformation and slow cancer cell growth by mechanisms independent of cyclooxygenase (COX) inhibition. Certain NSAIDs trigger the endoplasmic reticulum stress response (ERSR), as revealed by upregulation of molecular chaperones such as GRP78 and C/EBP homologous protein (CHOP). Although celecoxib (CELE) inhibits the sarcoendoplasmic reticulum Ca(2+) ATPase (SERCA), an effect known to induce ERSR, sulindac sulfide (SS) has not been reported to affect SERCA. Here, we investigated these two drugs for their effects on Ca(2+) homeostasis, ERSR, and glioma cell survival. Our findings indicate that SS is a reversible inhibitor of SERCA and that both SS and CELE bind SERCA at its cyclopiazonic acid binding site. Furthermore, CELE releases additional Ca(2+) from the mitochondria. In glioma cells, both NSAIDS upregulate GRP78 and activate ER-associated caspase-4 and caspase-3. Although only CELE upregulates the expression of CHOP, it appears that CHOP induction could be associated with mitochondrial poisoning. In addition, CHOP induction appears to be uncorrelated with the gliotoxicity of these NSAIDS in our experiments. Our data suggest that activation of ERSR is primarily responsible for the gliotoxic effect of these NSAIDS. Because SS has good brain bioavailability, has lower COX-2 inhibition, and has no mitochondrial effects, it represents a more appealing molecular candidate than CELE to achieve gliotoxicity via activation of ERSR.
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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.