Ibuprofen and nimesulide derivatives selectively induce apoptosis in HER2-positive breast cancer via inhibition of the PLA₂–COX-2–NF-κB pathway

Basit Öğe Kaydı
dc.authorid0000-0002-8506-2723
dc.authorid0000-0002-5664-1566
dc.authorid0000-0002-4181-7290
dc.authorid0000-0003-3892-2775
dc.authorid0000-0001-9405-8905
dc.authorid0000-0002-2793-6533
dc.contributor.authorÇakırlı, Egemen
dc.contributor.authorBedir, İpek
dc.contributor.authorBiliz, Yağmur
dc.contributor.authorYılmaz, Özgür
dc.contributor.authorKüçükgüzel, Şükriye Güniz
dc.contributor.authorTelci, Dilek
dc.date.accessioned2026-04-28T13:34:01Z
dc.date.available2026-04-28T13:34:01Z
dc.date.issued2026
dc.departmentFakülteler, Mühendislik ve Doğa Bilimleri Fakültesi, Kimya Mühendisliği Bölümü
dc.description.abstractBackground Chronic inflammation contributes to breast cancer development through the phospholipase A₂ (PLA₂)–cyclo oxygenase-2 (COX-2)–nuclear factor κB (NF-κB) cascade, which regulates prostaglandin synthesis, oxidative stress, and transcription of pro-inflammatory and anti-apoptotic genes. This pathway is particularly active in HER2-positive breast can cer, promoting proliferation, invasion, and resistance to apoptosis. Non-steroidal anti-inflammatory drugs such as ibuprofen and nimesulide target COX enzymes and have shown potential in suppressing inflammation-driven tumorigenesis. In this study, we evaluated the anticancer and anti-inflammatory activity of newly synthesized, structurally modified ibuprofen and nimesulide derivatives designed to modulate PLA₂–COX-2–NF-κB axis. Methods and Results Cytotoxicity was assessed in HER2-positive breast cancer cells (AU565 and SKBR3) and compared with normal dermal fibroblasts (HDF) and breast epithelial cells (MCF-12A), using WST-1 assays. Apoptosis, cell cycle distribution, caspase-3/7 activation, and ROS generation were analyzed by imaging-based assays, flow cytometry, and fluo rescence methods. Gene expression of PLA2G2A and PTGS2 was quantified by qRT-PCR, and NF-κB translocation was analyzed by immunocytochemistry. Two ibuprofen triazole derivative (D1) and ibuprofen thioether derivative (D7) and one nimesulide derivative (D8) significantly reduced cell viability in a dose-dependent manner without affecting normal cells. These derivatives induced G₀/G₁ arrest, caspase-3/7 activation, ROS reduction, and increased late apoptosis. Downregula tion of PLA2G2A and PTGS2 expression and inhibition of NF-κB translocation confirmed disruption of the PLA₂–COX-2– NF-κB cascade. Conclusion These findings demonstrate that structurally optimized ibuprofen and nimesulide derivatives exert dual anti inflammatory and anticancer effects in HER2-positive breast cancer by suppressing PLA₂–COX-2–NF-κB pathway and promoting apoptotic cell death.
dc.description.sponsorshipOpen access funding provided by the Scientific and Tech nological Research Council of Türkiye (TÜBİTAK). This work was supported by the Scientific and Technological Research Council of Turkiye (TÜBİTAK, Grant No. 124Z706) and by the Health Institutes of Türkiye (TÜSEB, Grant No. 4235). Bu çalışma, Türkiye Bilim ve Teknolojik Araştırma Konseyi (TÜBİTAK) tarafından sağlanan açık erişim fonuyla desteklenmiştir. Bu çalışma, Türkiye Bilim ve Teknolojik Araştırma Konseyi (TÜBİTAK, 124Z706 No'lu Hibe) ve Türkiye Sağlık Enstitüleri (TÜSEB, 4235 No'lu Hibe) tarafından desteklenmiştir.
dc.identifier.citationÇakırlı, E., Bedir, İ., Biliz, Y., Yılmaz, Ö., Küçükgüzel, Ş. G., & Telci, D. (2026). Ibuprofen and nimesulide derivatives selectively induce apoptosis in HER2-positive breast cancer via inhibition of the PLA₂–COX-2–NF-κB pathway. Molecular Biology Reports, 53(1), pp. 1-13. https://doi.org/10.1007/s11033-026-11835-6
dc.identifier.doi10.1007/s11033-026-11835-6
dc.identifier.endpage13
dc.identifier.issn1573-4978
dc.identifier.issn0301-4851
dc.identifier.issue1
dc.identifier.pmidPMID: 42029849
dc.identifier.scopusqualityQ2
dc.identifier.startpage1
dc.identifier.urihttps://doi.org/10.1007/s11033-026-11835-6
dc.identifier.urihttps://hdl.handle.net/20.500.13055/1450
dc.identifier.volume53
dc.identifier.wosqualityQ3
dc.indekslendigikaynakWeb of Science
dc.indekslendigikaynakScopus
dc.indekslendigikaynakPubMed
dc.indekslendigikaynak.otherSCI-E - Science Citation Index Expanded
dc.institutionauthorBiliz, Yağmur
dc.institutionauthorid0000-0002-4181-7290
dc.language.isoen
dc.publisherSpringer Nature Link
dc.relation.ispartofMolecular Biology Reports
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanı
dc.rightsinfo:eu-repo/semantics/openAccess
dc.subjectHER2-Positive Breast Cancer
dc.subjectIbuprofen
dc.subjectNimesulide
dc.subjectApoptosis
dc.subjectROS Reduction
dc.titleIbuprofen and nimesulide derivatives selectively induce apoptosis in HER2-positive breast cancer via inhibition of the PLA₂–COX-2–NF-κB pathway
dc.typeArticle
dspace.entity.typePublication

Dosyalar

Orijinal paket
Listeleniyor 1 - 1 / 1
Kapalı Erişim
İsim:
Tam Metin / Full Text.pdf
Boyut:
1.98 MB
Biçim:
Adobe Portable Document Format
İndir
Lisans paketi
Listeleniyor 1 - 1 / 1
Kapalı Erişim
İsim:
license.txt
Boyut:
1.17 KB
Biçim:
Item-specific license agreed upon to submission
Açıklama:
İndir

Koleksiyon

Kimya Mühendisliği Bölümü Koleksiyonu
PubMed İndeksli Yayın Koleksiyonu