ArticleOncogene2003
Cyclooxygenase-2 (COX-2) inhibitors sensitize tumor cells specifically to death receptor-induced apoptosis independently of COX-2 inhibition.
Article in Oncogene, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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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.
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Who cites it
32 citing papers in PubMed, 90 citations in OpenAlex.
- Exploring the Structure-Activity Relationship of COX Inhibitors with Anticancer Effects: A Comprehensive Review.Current topics in medicinal chemistry · 2025Review
- Signaling controversy and future therapeutical perspectives of targeting sphingolipid network in cancer immune editing and resistance to tumor necrosis factor-α immunotherapy.Cell communication and signaling : CCS · 2024Review
- Nimesulide, a COX-2 inhibitor, sensitizes pancreatic cancer cells to TRAIL-induced apoptosis by promoting DR5 clustering †.Cancer biology & therapy · 2023Article
- Effects of selective cyclooxygenase-2 inhibitor robenacoxib on primary cells derived from feline injection-site sarcoma.Journal of cellular and molecular medicine · 2023Article
- Firocoxib as a Potential Neoadjuvant Treatment in Canine Patients with Triple-Negative Mammary Gland Tumors.Animals : an open access journal from MDPI · 2022Article
- Methoxybenzamide derivative of nimesulide from anti-fever to anti-cancer: Chemical characterization and cytotoxicity.Saudi pharmaceutical journal : SPJ : the official publication of the Saudi Pharmaceutical Society · 2022Article
- Chemoprevention in Barrett's esophagus and esophageal adenocarcinoma.Therapeutic advances in gastroenterology · 2021Review
- Pharmacogenomics of 5-fluorouracil in colorectal cancer: review and update.Cellular oncology (Dordrecht, Netherlands) · 2020Review
- α-bisabolol enhances radiotherapy-induced apoptosis in endometrial cancer cells by reducing the effect of XIAP on inhibiting caspase-3.Bioscience reports · 2019Article
- Aza-BODIPY probe for selective visualization of cyclooxygenase-2 in cancer cells.RSC advances · 2019Article
- Involvement of NF-κB in mediating the anti-tumour effects of combretastatins in T cells.Investigational new drugs · 2018Article
- Article
- Therapeutic potential of cyclooxygenase-3 inhibitors in the management of glioblastoma.Journal of neuro-oncology · 2016Article
- Potency of non-steroidal anti-inflammatory drugs in chemotherapy.Molecular and clinical oncology · 2015Article
- Niflumic acid exhibits anti-tumor activity in nasopharyngeal carcinoma cells through affecting the expression of ERK1/2 and the activity of MMP2 and MMP9.International journal of clinical and experimental pathology · 2015Article
- Cyclooxygenase-2 and the inflammogenesis of breast cancer.World journal of clinical oncology · 2014Review
- Niflumic acid affects store-operated Ca(2+)-permeable (SOC) and Ca (2+)-dependent K (+) and Cl (-) ion channels and induces apoptosis in K562 cells.The Journal of membrane biology · 2014Article
- Role of chemoprophylaxis with either NSAIDs or statins in patients with Barrett's esophagus.World journal of gastrointestinal pharmacology and therapeutics · 2014Review
- Article
- Cyclooxygenase-1 and -2: molecular targets for cervical neoplasia.Journal of cancer prevention · 2013Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cyclooxygenase-2 (COX-2) is involved in diverse processes such as inflammation, carcinogenesis and apoptosis. As COX-2 inhibitors interfere with these processes, inhibition of COX-2 has been suggested as a promising anticancer treatment. However, the role of COX-2 in modulation of apoptosis as well as the death pathways affected by COX-2 inhibitors are poorly characterized. Here we demonstrate that the selective COX-2 inhibitors NS-398 and nimesulide increased TNF sensitivity of TNF-resistant HeLa H21 and TNF-sensitive HeLa D98 cells, although this cytokine induced significant COX-2 activity, as judged by prostaglandin E(2) (PGE(2)) production, only in H21 cells. TNF did also not induce PGE(2) production in MCF-7/casp-3 cells stably expressing COX-2; however, nimesulide strongly enhanced TNF-induced apoptosis in these cells. Furthermore, COX-2 activity in HeLa H21 cells could be inhibited by NS-398 concentrations that were 10 000-fold lower compared to those required for the induction of cell death. Most intriguingly, sensibilization to apoptosis was specifically observed in response to activation of death receptors. Not only TNF-induced cell death but also apoptosis triggered by the CD95 and TRAIL receptors was enhanced by nimesulide. In contrast, apoptosis induced by the anticancer drugs doxorubicine and etoposide that target the mitochondrial death pathway remained unaffected. Together, our data suggest that COX-2 inhibitors overcome apoptosis resistance and selectively sensitize tumor cells to the extrinsic death receptor-induced apoptotic pathway independently of COX-2.
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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.