Meme Kanseri Hücrelerinde Eş Zamanlı Epigenetik ve Epitranskriptomik Müdahalenin Etkisi

Yıl 2024, Sayı: 23, 505 - 521, 31.08.2024

Sevinç Yanar , Asuman Deveci Özkan , Merve Gülşen Bal Albayrak , Zeynep Betts

Öz

Amaç: Dünya çapında önemli bir ölüm nedeni olmaya devam etmekte olan meme kanseri için yenilikçi tedavi yaklaşımlarının geliştirilmesi gerekmektedir. Epigenetik ve epitranskriptomik düzenleme, yeni tedaviler için umut verici yollar olarak ortaya çıkmıştır. Sodyum Butirat (NaB) ve Meklofenamik Asit (MFA), epigenetik ve epitranskriptomik modülasyondaki ilgili rollerinden dolayı dikkat çekmektedir. Bir histon deasetilaz inhibitörü olan NaB, kromatin yeniden yapılanması ve gen ekspresyonunda kritik bir düzenleyici olarak görev yapmaktadır. MFA'nın ise FTO enziminin güçlü bir inhibitörü olduğu tespit edilmiştir. Bu inhibitör potansiyel, epitranskriptomik düzenlemedeki rolünü göstermektedir. Bu çalışma, MFA ve NaB'nin ayrı ayrı ve kombinasyon halinde MCF7 meme kanseri hücre hattı üzerindeki potansiyel etkilerini araştırmayı amaçlanmıştır.
Yöntem: MFA ve NaB kombinasyon tedavisinin sitotoksik ve apoptotik etkilerini araştırmak amacıyla hücre canlılığı analizi, Annexin V analizi ve Akridin Orange/DAPI boyaması yapılmıştır.
Bulgular: Sonuçlar kombinasyon tedavisinin beklenmedik şekilde antagonistik etki gösterdiğini ortaya çıkarmıştır. MFA ve NaB’ın tek başına uygulamasına kıyasla kombinasyon halinde uygulanması hücre canlılığında kayda değer bir artışa ve apoptotik yanıtın azalmasına neden olmuştur. En güçlü antagonistik etki, hücreler 48 saat boyunca 100 μM MFA ve 2 mM NaB ile inkübe edildiğinde gözlemlenmiştir (CI= 88,3).
Sonuç: Bu çalışma, ilk kez, meklofenamik asit ile sodyum bütirat arasındaki karmaşık etkileşime ışık tutmuş ve MCF7 meme kanseri hücreleri üzerindeki beklenmedik antagonistik etkisini ortaya koymuştur. Bu bulgular, geleneksel sinerjistik etkileşim kavramlarına meydan okumakla birlikte meme kanseri tedavisinde ilaç kombinasyonlarının karmaşıklığının altını çizmektedir.

Anahtar Kelimeler

Meme kanseri, meklofenamik asit, sodyum bütirat, kombinasyon tedavisi, antagonizm

The Impact of Simultaneous Epigenetic and Epitranscriptomic Intervention in Breast Cancer Cells

Öz

Aim: Breast cancer remains a significant cause of mortality worldwide, necessitating the development of innovative therapeutic approaches. Epigenetic and epitranscriptomic regulation have emerged as promising avenues for novel treatments. Sodium Butyrate (NaB) and Meclofenamic Acid (MFA) have gained attention for their respective roles in epigenetic and epitranscriptomic modulation. NaB, a histone deacetylase inhibitor, serves as a critical regulator of chromatin remodeling and gene expression. MFA has been identified to be a potent inhibitor of the FTO enzyme. This inhibitory potential marks its role in epitranscriptomic regulation. This study aimed to investigate the potential effects of MFA and NaB, individually and in combination, on the MCF7 breast cancer cell line.
Method: In order to investigate the cytotoxic and apoptotic effects of the combination treatment of MFA and NaB, cell viability assay, Annexin V analysis and Acridine Orange/DAPI staining were executed.
Results: The results revealed that the combination treatment unexpectedly exhibited antagonistic effects. This was evidenced by a remarkable increase in cell viability and a decreased apoptotic response compared to individual treatments. The strongest antagonistic effect was observed when the cells were treated with 100 μM MFA and 2 mM NaB for a period of 48 hours (CI = 88.3).
Conclusion: This study, for the first time, sheds light on the complex interaction between meclofenamic acid and sodium butyrate that reveals an unexpected antagonistic effect on MCF7 breast cancer cells. These findings challenge conventional concepts of synergistic interactions and underscore the complexity of drug combinations in breast cancer treatment.

Anahtar Kelimeler

Breast cancer, meclofenamic acid, sodium butyrate, combined therapy, antagonism

Kaynakça

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