ArticleOncogene2008
Decisive role of cyclooxygenase-2 and lipocalin-type prostaglandin D synthase in chemotherapeutics-induced apoptosis of human cervical carcinoma cells.
Article in Oncogene, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 32 citations in OpenAlex.
- Cannabigerol and Cannabichromene Induce Lung Cancer Cell Death and Apoptosis-Contribution of PPARα to Cannabigerol Effects.Antioxidants (Basel, Switzerland) · 2026Article
- Review
- Cannabinoids as anticancer drugs: current status of preclinical research.British journal of cancer · 2022Review
- MSC-Derived Extracellular Vesicle-Delivered L-PGDS Inhibit Gastric Cancer Progression by Suppressing Cancer Cell Stemness and STAT3 Phosphorylation.Stem cells international · 2022Article
- Biochemical and Structural Characteristics, Gene Regulation, Physiological, Pathological and Clinical Features of Lipocalin-Type Prostaglandin DFrontiers in physiology · 2021Review
- Tumour-Infiltrating Immune Cell-Based Subtyping and Signature Gene Analysis in Breast Cancer Based on Gene Expression Profiles.Journal of Cancer · 2020Article
- Gene expression profiles analysis identifies a novel two-gene signature to predict overall survival in diffuse large B-cell lymphoma.Bioscience reports · 2019Article
- Lovastatin lactone elicits human lung cancer cell apoptosis via a COX-2/PPARγ-dependent pathway.Oncotarget · 2016Article
- Induction but not inhibition of COX-2 confers human lung cancer cell apoptosis by celecoxib.Journal of lipid research · 2013Article
- Resolution of inflammation as a novel chemopreventive strategy.Seminars in immunopathology · 2013Review
- Article
- Modulation of mammary cancer cell migration by 15-deoxy-delta(12,14)-prostaglandin J(2): implications for anti-metastatic therapy.The Biochemical journal · 2010Article
- Prostaglandin (PG)D(2) and 15-deoxy-Delta(12,14)-PGJ(2), but not PGE(2), mediate shear-induced chondrocyte apoptosis via protein kinase A-dependent regulation of polo-like kinases.Cell death and differentiation · 2010Article
- The use of Cox-2 and PPARγ signaling in anti-cancer therapies.Experimental and therapeutic medicine · 2010Article
- Enhancement of 5-fluorouracil efficacy on high COX-2 expressing HCA-7 cells by low dose indomethacin and NS-398 but not on low COX-2 expressing HT-29 cells.Pathology oncology research : POR · 2009Article
- Celecoxib antagonizes perifosine's anticancer activity involving a cyclooxygenase-2-dependent mechanism.Molecular cancer therapeutics · 2009Article
- R(+)-methanandamide-induced apoptosis of human cervical carcinoma cells involves a cyclooxygenase-2-dependent pathway.Pharmaceutical research · 2009Article
- Nanotechnology of emerging targeting systems.Minerva biotecnologica · 2008Article
- PPARgamma and Apoptosis in Cancer.PPAR research · 2008Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The role of cyclooxygenase-2 (COX-2) in cancer remains controversial. Using cervical carcinoma cells (HeLa), the present study investigates the involvement of COX-2 in apoptosis elicited by the chemotherapeutics paclitaxel, cisplatin and 5-fluorouracil. Each compound led to a profound induction of COX-2 expression and prostaglandin (PG) synthesis, accompanied by a substantial decrease of viability and enhanced apoptosis. Cells were significantly less sensitive to apoptotic death when either COX-2 expression or its activity was suppressed by small-interfering RNA (siRNA) and by the selective COX-2 inhibitor NS-398, respectively. Experiments performed to clarify how COX-2 leads to apoptosis revealed a profound proapoptotic action of PGD2 and its dehydration product, 15-deoxy-Delta(12,14) PGJ2 (15d-PGJ2). In line with these findings, chemotherapeutics-induced apoptosis was prevented by siRNA targeting lipocalin-type PGD synthase (L-PGDS), which catalyses the isomerization of PGH(2) to PGD2. Moreover, apoptosis by chemotherapeutics, PGD2 and 15d-PGJ2 was suppressed by the peroxisome proliferator-activated receptor gamma (PPARgamma) antagonist, GW-9662 or PPARgamma siRNA. Finally, a COX-2-dependent apoptotic mechanism of all investigated chemotherapeutics was confirmed in human lung cancer cells (A549) as well as in another cervical carcinoma cell line (C33A). Collectively, this study suggests COX-2 induction and synthesis of L-PGDS-derived, PPARgamma-activating PGs as a decisive target by which several chemotherapeutics induce apoptosis. COX-2 is therefore suspected to sensitize cancer cells to apoptotic death under certain circumstances, suggesting that COX-2 inhibition during cancer therapy could diminish its efficacy.
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