Epigallokateşin-3- gallat uygulamasına bağlı olarak kronik miyeloid lösemi hücrelerinde genetik ve epigenetik otofaji regülatörlerinin ekspresyon değişimlerinin değerlendirilmesi

Year 2019, Volume: 26 Issue: 1, 57 - 66, 04.03.2019

Çığır Biray Avcı , Bakiye Göker Bağca

https://doi.org/10.17343/sdutfd.469847

Abstract

Amaç:
Kronik miyeloid lösemi, Bcr-Abl1 füzyon tirozin kinazının oluşumu aktivitesi
ile tanımlanır. Füzyon proteinini hedefleyen inhibitörün keşfi sağ kalım
oranlarında büyük artış meydana getirmiştir. Ancak bu inhibitöre karşı direnç
gelişimi yeni terapi hedeflerinin belirlenmesini zorunlu kılmaktadır. Otofaji,
güncel kanser araştırmalarında dikkat çekici bir iki yönlü hedeftir. Kanser
hücrelerini stres koşullarına adapte etmeyi sağladığı için genellikle
otofajinin inhibisyou hedeflenmektedir. Epigallokateşin-3-gallat yeşil çayda
bulunan temel bir fitokimyasaldır. mikroRNA’lar gibi epigenetik regülatörlerin
üzerindeki etkinliği tedavide olduğu kadar hastaların beslenme önerilerinin
düzenlenmesinde de önem taşımaktadır. Bu çalışmada bir flavanoid olan
epigallokateşin-3-gallatın kronik miyeloid lösemi hücrelerinde otofajiyi
düzenleyen genetik ve epigenetik faktörler üzerindeki etkinliğinin
araştırılması amaçlanmıştır.

Gereç ve yöntem: mikroRNA-mRNA
etkileşimini değerlendiren veritabanları kullanılarak otofaji ilişkili genleri
hedefleyen mikroRNA’lar belirlenmiştir. 50 µikromolar Epigallokateşin-3-gallat
uygulanan K-562 hücrelerinde gerçek zamanlı kantitatif PCR yöntemi kullanılarak
otofaji ilişkili genlerin ve bu genleri hedefleyen mikroRNA’ların ekspresyon
seviyeleri belirlenmiştir.

Bulgular:
Epigallokateşin-3-gallat uygulaması K-562 hücrelerinde otofajinin pozitif
regülatörü olan genlerin ekspresyon seviyesinde anlamlı azalışa, bu genleri
hedefleyen mikroRNA’ların ekspresyon seviyelerinde ise anlamlı artışa neden olmuştur.

Sonuç:
Elde edilen veriler doğrultusunda epigallokateşin-3-gallatın, kronik miyeloid
lösemi hücrelerinde genetik ve epigenetik regülasyonla otofaji inhibisyonuna
neden olduğu belirlenmiştir. Otofajinin çift yönlü mekanizması göz önünde
bulundurulduğunda bu sonuç epigallokateşin-3-gallatın ilaç potansiyeli olma
konusunda olduğu kadar hastaların beslenme şeklinde de önem taşıyan bir
kimyasal olduğu gerçeğini ortaya koymaktadır.

Keywords

Kronik Miyeloid Lösemi, miRNA, Otofaji

Evaluation of expression changes of genetic and epigenetic autophagy regulators in chronic myeloid leukemia cells due to epigallocatechin-3-gallate treatment

Abstract

Purpose: Chronic myeloid leukemia is characterized by the
formation and activation of Bcr-Abl1 fusion tyrosine kinase. Discovery of the
inhibitor which targets the fusion protein results in a significant increase in
survival rates.  However the development
of resistance to the inhibitor necessitates determining new therapy targets.
Autophagy is a remarkable dual target in recent cancer researches. It is
usually aimed at inhibition of autophagy because autophagy allows cells to
adapt to stress conditions. Epigallocatechin-3-gallate is a basic phytochemical
found in green tea. The efficacy of epigenetic regulators, such as microRNAs,
is important in the regulation of dietary recommendations as well as in
treatment. In this study, it was aimed to investigate the effect of
epigallocatechin-3-gallate, a flavanoid, on genetic and epigenetic factors
regulating autophagy in chronic myeloid leukemia cells.

Materials
and methods: microRNAs
which are target autophagy-related genes have been identified using appropriate
databases. Expression levels of autophagy-related genes and microRNAs targeting
these genes were determined using real-time quantitative PCR method in 50
micromolar Epigallocatechin-3-gallate treated K-562 cells.

Results: Epigallocatechin-3-gallate treatment resulted in a
significant decrease and increase the expression levels of autophagy-related
genes 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 genetic
and epigenetic regulation in chronic myeloid leukemia cells.
Considering the dual
mechanism of autophagy, this result suggests that epigallocatechin-3-gallate is
a chemical that is important for the nutrition of patients as well as its
potential to be used as a drug.

Keywords

Chronic Myeloid Leukemia, miRNA, Autophagy

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