sdü tıp fak derg Medical Journal of Süleyman Demirel University 2602-2109 Süleyman Demirel Üniversitesi 10.17343/sdutfd.469847 Clinical Sciences Klinik Tıp Bilimleri Epigallokateşin-3- gallat uygulamasına bağlı olarak kronik miyeloid lösemi hücrelerinde genetik ve epigenetik otofaji regülatörlerinin ekspresyon değişimlerinin değerlendirilmesi Evaluation of expression changes of genetic and epigenetic autophagy regulators in chronic myeloid leukemia cells due to epigallocatechin-3-gallate treatment https://orcid.org/0000-0002-2748-3124 Biray Avcı Çığır EGE ÜNİVERSİTESİ, TIP FAKÜLTESİ, TEMEL TIP BİLİMLERİ BÖLÜMÜ, TIBBİ BİYOLOJİ ANABİLİM DALI https://orcid.org/0000-0002-5714-7455 Göker Bağca Bakiye EGE ÜNİVERSİTESİ, TIP FAKÜLTESİ, TEMEL TIP BİLİMLERİ BÖLÜMÜ, TIBBİ BİYOLOJİ ANABİLİM DALI 03 04 2019 26 1 57 66 10 12 2018 11 06 2018 Copyright © 1994, Süleyman Demirel Üniversitesi Tıp Fakültesi Dergisi 1994 Süleyman Demirel Üniversitesi Tıp Fakültesi Dergisi

Amaç:Kronik miyeloid lösemi, Bcr-Abl1 füzyon tirozin kinazının oluşumu aktivitesiile tanımlanır. Füzyon proteinini hedefleyen inhibitörün keşfi sağ kalımoranlarında büyük artış meydana getirmiştir. Ancak bu inhibitöre karşı dirençgelişimi yeni terapi hedeflerinin belirlenmesini zorunlu kılmaktadır. Otofaji,güncel kanser araştırmalarında dikkat çekici bir iki yönlü hedeftir. Kanserhücrelerini stres koşullarına adapte etmeyi sağladığı için genellikleotofajinin inhibisyou hedeflenmektedir. Epigallokateşin-3-gallat yeşil çaydabulunan temel bir fitokimyasaldır. mikroRNA’lar gibi epigenetik regülatörlerinüzerindeki etkinliği tedavide olduğu kadar hastaların beslenme önerilerinindüzenlenmesinde de önem taşımaktadır. Bu çalışmada bir flavanoid olanepigallokateşin-3-gallatın kronik miyeloid lösemi hücrelerinde otofajiyidüzenleyen genetik ve epigenetik faktörler üzerindeki etkinliğininaraştırılması amaçlanmıştır. Gereç ve yöntem: mikroRNA-mRNAetkileşimini değerlendiren veritabanları kullanılarak otofaji ilişkili genlerihedefleyen mikroRNA’lar belirlenmiştir. 50 µikromolar Epigallokateşin-3-gallatuygulanan K-562 hücrelerinde gerçek zamanlı kantitatif PCR yöntemi kullanılarakotofaji ilişkili genlerin ve bu genleri hedefleyen mikroRNA’ların ekspresyonseviyeleri belirlenmiştir.Bulgular:Epigallokateşin-3-gallat uygulaması K-562 hücrelerinde otofajinin pozitifregülatörü olan genlerin ekspresyon seviyesinde anlamlı azalışa, bu genlerihedefleyen mikroRNA’ların ekspresyon seviyelerinde ise anlamlı artışa neden olmuştur.Sonuç:Elde edilen veriler doğrultusunda epigallokateşin-3-gallatın, kronik miyeloidlösemi hücrelerinde genetik ve epigenetik regülasyonla otofaji inhibisyonunaneden olduğu belirlenmiştir. Otofajinin çift yönlü mekanizması göz önündebulundurulduğunda bu sonuç epigallokateşin-3-gallatın ilaç potansiyeli olmakonusunda olduğu kadar hastaların beslenme şeklinde de önem taşıyan birkimyasal olduğu gerçeğini ortaya koymaktadır.

Purpose: Chronic myeloid leukemia is characterized by theformation and activation of Bcr-Abl1 fusion tyrosine kinase. Discovery of theinhibitor which targets the fusion protein results in a significant increase insurvival rates. However the developmentof resistance to the inhibitor necessitates determining new therapy targets.Autophagy is a remarkable dual target in recent cancer researches. It isusually aimed at inhibition of autophagy because autophagy allows cells toadapt to stress conditions. Epigallocatechin-3-gallate is a basic phytochemicalfound in green tea. The efficacy of epigenetic regulators, such as microRNAs,is important in the regulation of dietary recommendations as well as intreatment. In this study, it was aimed to investigate the effect ofepigallocatechin-3-gallate, a flavanoid, on genetic and epigenetic factorsregulating autophagy in chronic myeloid leukemia cells.Materialsand methods: microRNAswhich are target autophagy-related genes have been identified using appropriatedatabases. Expression levels of autophagy-related genes and microRNAs targetingthese genes were determined using real-time quantitative PCR method in 50micromolar Epigallocatechin-3-gallate treated K-562 cells.Results: Epigallocatechin-3-gallate treatment resulted in asignificant decrease and increase the expression levels of autophagy-relatedgenes and microRNAs targeting these genes in K-562 cells, respectively.Conclusion: In the direction of the results,epigallocatechin-3-gallate was found to cause autophagy inhibition by geneticand epigenetic regulation in chronic myeloid leukemia cells.Considering the dualmechanism of autophagy, this result suggests that epigallocatechin-3-gallate isa chemical that is important for the nutrition of patients as well as itspotential to be used as a drug.

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