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Journals / Hitit Medical Journal / 2026 / Cilt: 8 Sayı: 3

Differential Gene Expression Induced by Carvacrol in MCF-7 and MDA-MB-231 Breast Cancer Cells

Karvakrolün MCF-7 ve MDA-MB-231 Meme Kanseri Hücrelerinde İndüklediği Diferansiyel Gen Ekspresyon Değişiklikleri

Asmaa Abuaisha(BIRUNI UNIVERSITY, FACULTY OF ENGINEERING AND NATURAL SCIENCES, DEPARTMENT OF MOLECULAR BIOLOGY AND GENETICS, MOLECULAR BIOLOGY AND GENETICS PR. (FULL SCHOLARSHIP))0000-0003-2869-6620
Halil İbrahim Arslan(BIRUNI UNIVERSITY, BİRUNİ RESEARCH CENTER)0009-0001-4172-4748
Kübra Coşkun(BIRUNI UNIVERSITY, BİRUNİ RESEARCH CENTER)0009-0002-3232-0984
Emir Nekay(BIRUNI UNIVERSITY, SCHOOL OF MEDICINE, DEPARTMENT OF SURGICAL MEDICAL SCIENCES, DEPARTMENT OF GENERAL SURGERY)0009-0001-2389-0486
Tugba Bayramoglu(BIRUNI UNIVERSITY)0009-0006-7185-5753
Cüneyd Yavaş(BIRUNI UNIVERSITY, FACULTY OF ENGINEERING AND NATURAL SCIENCES, DEPARTMENT OF MOLECULAR BIOLOGY AND GENETICS, MOLECULAR BIOLOGY AND GENETICS PR. (ENGLISH))0000-0002-1597-5922
Selman Emiroğlu(ISTANBUL UNIVERSITY, İSTANBUL FACULTY OF MEDICINE, DEPARTMENT OF SURGICAL MEDICAL SCIENCES, DEPARTMENT OF GENERAL SURGERY)0000-0001-9333-6926
Pages
687–699
Publication Date
2026-10-14
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AI Summary & Key Takeaways

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

Overall survival (OS) and disease-free survival (DFS) analyses were conducted using GEPIA2 based on TCGA-BRCA data.

📌 3 Key Takeaways

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Objective & Hypothesis:Objective: Breast cancer (BC) is a heterogeneous malignancy driven by dysregulated molecular pathways that promote proliferation, invasion, and therapeutic resistance.
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Key Findings & Data:Carvacrol, a natural monoterpenoid phenol, has demonstrated anticancer potential; however, its subtype-specific molecular mechanisms in BC remain unclear.
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Conclusion & Impact:Overall survival (OS) and disease-free survival (DFS) analyses were conducted using GEPIA2 based on TCGA-BRCA data.
🔬Design:Araştırma Makalesi
📍Scope:Comprehensive Sample
⚙️Variables:Gen Ekspresyonu Modülasyonu · Karvakrol · Meme Kanseri

Abstract

Objective: Breast cancer (BC) is a heterogeneous malignancy driven by dysregulated molecular pathways that promote proliferation, invasion, and therapeutic resistance. Carvacrol, a natural monoterpenoid phenol, has demonstrated anticancer potential; however, its subtype-specific molecular mechanisms in BC remain unclear. Materials and Methods: This study combined bioinformatic and experimental approaches to evaluate the functional relationships and prognostic relevance of MKI67, E2F4, FOSL1, CD44, CDKN1A (P21), CASP9, ABCB1, ABCC1, and ABCC5. The STRING database was used to evaluate protein–protein interaction (PPI) networks. Overall survival (OS) and disease-free survival (DFS) analyses were conducted using GEPIA2 based on TCGA-BRCA data. MCF-7 and MDA-MB-231 BC cells were cultured and exposed to 400 µM carvacrol for 48 hours. Gene expression levels were evaluated by qPCR. Relative mRNA expression was calculated using the 2^−ΔΔCt method. Results: PPI analysis revealed significant functional connectivity among the studied genes (p=2.15 e−09). Survival analyses did not demonstrate consistent independent prognostic significance. Carvacrol induced subtype-dependent molecular alterations. In MCF-7 cells, CD44, FOSL1, and MKI67 were significantly downregulated (p<0.05), indicating suppression of proliferative and invasive pathways. In MDA-MB-231 cells, P21 expression was significantly upregulated (p=0.006), suggesting the induction of cell cycle arrest in this aggressive phenotype. No significant changes were observed in E2F4, CASP9, ABCB1, ABCC1, or ABCC5 expression. Conclusion: Carvacrol induces subtype-specific alterations in the expression of the studied genes (CD44, FOSL1, MKI67, and P21) in BC cells. These findings provide preliminary molecular evidence of its biological activity and warrant further protein-based analyses, functional in vitro experiments, and in vivo studies to elucidate its potential therapeutic role in BC.

Özet

Amaç: Meme kanseri, proliferasyon, invazyon ve tedavi direncini artıran düzensiz moleküler yolaklar tarafından yönlendirilen heterojen bir malignitedir. Doğal bir monoterpenoid fenol olan karvakrol, antikanser potansiyel göstermiştir; ancak meme kanserindeki alt tip-spesifik moleküler mekanizmaları henüz tam olarak aydınlatılamamıştır. Gereç ve Yöntem: Bu çalışmada, MKI67, E2F4, FOSL1, CD44, CDKN1A (P21), CASP9, ABCB1, ABCC1 ve ABCC5 genlerinin fonksiyonel ilişkileri ve prognostik önemi biyoinformatik ve deneysel yaklaşımlar birlikte kullanılarak değerlendirilmiştir. Protein-protein etkileşim (PPI) ağları STRING veritabanı kullanılarak analiz edilmiştir. Genel sağkalım ve hastalıksız sağkalım analizleri, TCGA-BRCA verilerine dayalı olarak GEPIA2 aracılığıyla gerçekleştirilmiştir. MCF-7 ve MDA-MB-231 meme kanseri hücreleri kültüre edilerek 48 saat boyunca 400 µM karvakrol ile muamele edilmiştir. Gen ekspresyon düzeyleri qPCR ile değerlendirilmiştir. Göreceli mRNA ekspresyonu 2^−ΔΔCt yöntemi kullanılarak hesaplanmıştır. Bulgular: PPI analizi, incelenen genler arasında anlamlı fonksiyonel bağlantılar bulunduğunu ortaya koymuştur (p=2.15e−09). Sağkalım analizleri, bu genlerin bağımsız prognostik önemini tutarlı bir şekilde göstermemiştir. Karvakrol, meme kanseri alt tiplerine bağlı olarak gen ekspresyonunda farklı değişikliklere neden olmuştur. MCF-7 hücrelerinde CD44, FOSL1 ve MKI67 genlerinin ekspresyon düzeyleri anlamlı olarak azalmıştır (p<0.05). MDA-MB-231 hücrelerinde ise P21 gen ekspresyonu anlamlı düzeyde artmıştır (p=0.006). Buna karşın E2F4, CASP9, ABCB1, ABCC1 ve ABCC5 genlerinin ekspresyon düzeylerinde istatistiksel olarak anlamlı bir değişiklik saptanmamıştır. Sonuç: Karvakrol, meme kanseri hücrelerinde incelenen genlerin (CD44, FOSL1, MKI67 ve P21) ekspresyonunda alt tipe özgü değişiklikler oluşturmuştur. Bu bulgular, karvakrolün biyolojik etkilerine ilişkin ön moleküler kanıtlar sağlamakta olup, meme kanserindeki terapötik potansiyelinin aydınlatılabilmesi için protein düzeyinde doğrulama çalışmaları, fonksiyonel in vitro deneyler ve in vivo araştırmalarla desteklenmesi gerekmektedir.

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Cite This Article

Abuaisha, A., Arslan, H. İ., Coşkun, K., Nekay, E., Bayramoglu, T., Yavaş, C., Emiroğlu, S. (2026). Differential Gene Expression Induced by Carvacrol in MCF-7 and MDA-MB-231 Breast Cancer Cells. Hitit Medical Journal, Cilt: 8 Sayı: 3, 687–699. https://doi.org/10.52827/hititmedj.1920844

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