Quercetin-Mediated Modulation of Tumor Suppressor miR-15a, miR-34a, and p53 Signaling in MCF-7 Breast Cancer Cells

Öz

Breast cancer remains one of the most prevalent types of cancer among women globally, contributing significantly to cancer-related mortality. Despite advancements in treatment, many cases continue to exhibit resistance to chemotherapy, radiotherapy, and hormonal therapies, often resulting in drug resistance, high recurrence rates, and severe side effects. Consequently, the role of the natural food components in cancer prevention and treatment is gaining increasing attention in modern medicine. This study focuses on quercetin, a phytochemical compound, and its effects on the breast cancer cell line MCF-7. Specifically, the study has investigated changes in the expression of miR-15a and miR-34a—microRNAs (miRNAs) known to regulate gene expression at the post-transcriptional level—and the P53 gene, which is critically involved in apoptosis. The analysis was performed using quantitative polymerase chain reaction (qPCR) and Western blot techniques. The results demonstrated that quercetin treatment at concentrations of 40 µM and 80 µM led to a 1.34-fold and 2.73-fold increase in P53 gene expression, respectively. Additionally, the tumor suppressor miRNA miR-15a showed expression changes of 1.48-fold and 1.69-fold at the same quercetin concentrations. Similarly, miR-34a expression levels increased by 1.23-fold and 1.39-fold at 40 µM and 80 µM, respectively. These findings suggest that dietary phytochemicals, such as quercetin, may have therapeutic potential by modulating miRNA expression and targeting the p53 pathway. In conclusion, quercetin emerges as a promising natural therapeutic agent for breast cancer, warranting further in vivo studies and clinical trials to confirm its efficacy and explore its potential as a part of combination therapies.

Anahtar Kelimeler

• Flavonoids
• cancer
• non-coding RNAs

MCF-7 Meme Kanseri Hücrelerinde Tümör Baskılayıcı miR-15a, miR-34a ve p53 Sinyalizasyonunun Kuersetin Aracılı Modülasyonu

Öz

Meme kanseri, küresel olarak kadınlarda en yaygın kanser türlerinden biri olmaya devam etmekte ve kanserle ilişkili ölümlere önemli ölçüde sebep olmaktadır. Tedavideki gelişmelere rağmen, birçok vaka kemoterapi, radyoterapi ve hormonal tedavilere direnç göstermeye devam etmekte ve bu da sıklıkla ilaç direnci, yüksek tekrarlama oranları ve ciddi yan etkilerle sonuçlanmaktadır. Bu nedenle, doğal gıda bileşenlerinin kanser önleme ve tedavisindeki rolü modern tıpta giderek daha fazla ilgi görmektedir. Bu çalışma, bir fitokimyasal bileşik olan kuersetin ve meme kanseri hücre hattı MCF-7 üzerindeki etkilerine odaklanmaktadır. Çalışmada, özellikle, gen ifadesini transkripsiyon sonrası düzeyde düzenlediği bilinen mikroRNA'lar (miRNA) olan miR-15a ve miR-34a'nın ve apoptozda kritik rol oynayan P53 geninin ifadesindeki değişiklikler araştırılmıştır. Analiz, kantitatif polimeraz zincir reaksiyonu (qPCR) ve Western blot teknikleri kullanılarak gerçekleştirilmiştir. Sonuçlar, 40 µM ve 80 µM konsantrasyonlarında kuersetin tedavisinin P53 gen ekspresyonunda sırasıyla 1,34 kat ve 2,73 kat artışa yol açtığını göstermiştir. Ek olarak, tümör baskılayıcı miRNA miR-15a aynı kuersetin konsantrasyonlarında 1,48 kat ve 1,69 kat ekspresyon değişiklikleri olduğu saptanmıştır. Benzer şekilde, miR-34a ekspresyon seviyeleri sırasıyla 40 µM ve 80 µM'de 1,23 kat ve 1,39 kat artmıştır. Bu bulgular, kuersetin gibi diyet fitokimyasallarının miRNA ekspresyonunu düzenleyerek ve p53 yolunu hedefleyerek terapötik potansiyele sahip olabileceğini düşündürmektedir. Sonuç olarak, kuersetin meme kanseri için umut verici bir doğal terapötik ajan olarak ortaya çıkmakta ve etkinliğini doğrulamak ve kombinasyon terapilerinin bir parçası olarak potansiyelini keşfetmek için daha fazla in vivo çalışma ve klinik denemeyi gerektirmektedir.

Anahtar Kelimeler

• Flavonoidler
• kanser
• kodlama yapmayan RNAlar
• P53

Kaynakça

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