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Journals / Acta Medica Nicomedia / 2026 / Cilt: 9

PARTHENOLIDE INDUCES FERROPTOSIS IN HEAD AND NECK SQUAMOUS CELL CARCINOMA THROUGH NF-κB INHIBITION AND NQO1 DOWNREGULATION

Baş ve Boyun Kanserlerinde Parthenolide'in NF-κB İnhibisyonu ve NQO1 Downregulation Aracılığıyla Ferroptoz İndüksiyonu

Negar Taghavi Pourianazar(ISTANBUL AYDIN UNIVERSITY)0000-0003-3250-1427
Pages
1–8
Publication Date
2026-10-27
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AI Summary & Key Takeaways

AI Insight
⚡ TL;DR(Too Long; Didn't Read)

These findings suggest that parthenolide is a promising candidate for ferroptosis-based therapy in head and neck squamous cell carcinoma.

📌 3 Key Takeaways

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Objective & Hypothesis:Objective: Ferroptosis resistance is a major obstacle in head and neck squamous cell carcinoma treatment.
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Key Findings & Data:This study investigated whether parthenolide can induce ferroptosis Methods: SCC-25 and HSC-3 head and neck squamous cell carcinoma cell lines were treated with parthenolide (0–50μM) for 24–72 hours.
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Conclusion & Impact:These findings suggest that parthenolide is a promising candidate for ferroptosis-based therapy in head and neck squamous cell carcinoma.
🔬Design:Araştırma Makalesi
📍Scope:Comprehensive Sample
⚙️Variables:Parthenolide · ferroptoz · reaktif oksijen türleri

Abstract

Objective: Ferroptosis resistance is a major obstacle in head and neck squamous cell carcinoma treatment. Parthenolide, a natural sesquiterpene lactone from Feverfew, exhibits anticancer activity. This study investigated whether parthenolide can induce ferroptosis Methods: SCC-25 and HSC-3 head and neck squamous cell carcinoma cell lines were treated with parthenolide (0–50μM) for 24–72 hours. Cell viability was evaluated using the methylthiazolyl tetrazolium assay. Intracellular reactive oxygen species levels were measured using a fluorescent probe assay. Gene expression was analyzed by quantitative real-time polymerase chain reaction. The involvement of ferroptosis was confirmed using the ferroptosis inhibitor ferrostatin-1. Results: Parthenolide reduced cell viability in a dose-dependent manner, with IC₅₀ values of 15–22μM at 48 hours. Intracellular reactive oxygen species (ROS) levels increased 2.1–2.8-fold following 25μM parthenolide treatment. Expression of ferroptosis resistance-related genes was significantly decreased. The expression levels of cystine/glutamate transporter subunit 11 (SLC7A11), glutathione peroxidase 4 (GPX4), and NAD(P)H quinone dehydrogenase 1 (NQO1) were reduced by 68–80%, 62–75%, and 78–90%, respectively. In contrast, the ferroptosis-promoting genes nuclear receptor coactivator 4 (NCOA4) and acyl-CoA synthetase long-chain family member 4 (ACSL4) were upregulated by 1.6–2.5-fold. Ferrostatin-1 significantly reversed parthenolide-induced cell death. Conclusion: Parthenolide induces ferroptosis in head and neck squamous cell carcinoma cells by promoting ROS accumulation, suppressing ferroptosis resistance genes, and activating ferroptosis-related genes. These findings suggest that parthenolide is a promising candidate for ferroptosis-based therapy in head and neck squamous cell carcinoma.

Özet

Amaç: Ferroptoz direnci, baş ve boyun skuamöz hücreli karsinomlarının tedavisinde önemli bir engel oluşturmaktadır. Parthenolide, Feverfew bitkisinden elde edilen doğal bir seskiterpen lakton bileşiğidir. Bu çalışmada parthenolide'in baş ve boyun skuamöz hücreli karsinom hücrelerinde ferroptozu indükleme ve ferroptoz direncini aşma potansiyeli araştırılmıştır. Yöntem: SCC-25 ve HSC-3 baş ve boyun skuamöz hücreli karsinom hücreleri 0–50µM parthenolide ile 24–72 saat boyunca muamele edilmiştir. Hücre canlılığı metiltiyazol tetrazolyum testi ile değerlendirilmiştir. Hücre içi reaktif oksijen türleri düzeyleri floresan prob yöntemiyle ölçülmüştür. Gen ekspresyonları kantitatif gerçek zamanlı polimeraz zincir reaksiyonu ile analiz edilmiştir. Ferroptozun rolü, ferroptoz inhibitörü ferrostatin-1 kullanılarak doğrulanmıştır. Bulgular: Parthenolide, hücre canlılığını doza bağlı olarak azaltmış ve 48 saatte IC₅₀ değeri 15–22µM arasında bulunmuştur. Hücre içi reaktif oksijen türleri düzeyleri 25µM parthenolide uygulamasında 2,1–2,8 kat artmıştır. Ferroptoz direnci ile ilişkili genlerin ekspresyonunda belirgin azalma saptanmıştır. Sistin/glutamat taşıyıcısı alt birimi 11 (SLC7A11), glutatyon peroksidaz 4 (GPX4) ve NAD(P)H kinon dehidrogenaz 1 (NQO1) genlerinin ekspresyonları sırasıyla %68–80, %62–75 ve %78–90 oranında azalmıştır. Buna karşılık, ferroptozu destekleyen nükleer reseptör koaktivatörü 4 (NCOA4) ve açil-koenzim A sentetaz uzun zincir aile üyesi 4 (ACSL4) genlerinin ekspresyonları 1,6–2,5 kat artmıştır. Ferrostatin-1 uygulaması parthenolide kaynaklı hücre ölümünü önemli ölçüde geri çevirmiştir. Sonuç: Parthenolide, baş ve boyun skuamöz hücreli karsinom hücrelerinde reaktif oksijen türlerinin birikimini artırarak ferroptoz direnciyle ilişkili genleri baskılamakta ve ferroptozu destekleyen genleri aktive etmektedir. Bulgular, parthenolide'in ferroptoz temelli tedavi yaklaşımlarında potansiyel bir terapötik ajan olabileceğini göstermektedir.

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Cite This Article

Pourianazar, N. T. (2026). PARTHENOLIDE INDUCES FERROPTOSIS IN HEAD AND NECK SQUAMOUS CELL CARCINOMA THROUGH NF-κB INHIBITION AND NQO1 DOWNREGULATION. Acta Medica Nicomedia, Cilt: 9, 1–8. https://doi.org/10.53446/actamednicomedia.1930117

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