Monensinin Glioblastoma Multiformede Kaspaz-10 Aracılı Apoptoz Üzerine Etkileri

Abstract

Glioblastoma multiforme (GBM), en kötü huylu primer merkezi sinir sistemi tümörüdür. Şu anda, GBM için iyileştirici tedavi seçenekleri yoktur ve 5 yıllık hayatta kalma oranı %5’den daha azdır. Monensin, ‘’Streptomyces cinnamonensis’’ den elde edilen antibakteriyal ve antiparazitik etkileri bilinen iyonofor bir antibiyotiktir. Literatürde monensinin GBM hücrelerinin apoptoz mekanizması üzerine etki gösterdiği bir çalışmaya rastlanmadığından yapılan bu çalışmanın amacı monensinin U373 GBM hücrelerinde apoptoz aracılı hücre proliferasyonu üzerine etkilerini araştırmaktır. Monensinin U373 hücre canlılığı üzerine etkileri XTT ile apoptoz üzerine etkileri ise RT-PCR ve Annexin V ile araştırılmıştır. Monensinin U373 GBM hücrelerinde IC50 değeri 48’inci saatte 4 μM olarak bulunmuştur. Monensin U373 GBM hücrelerinde apoptoz oranında 6 katlık bir artışa neden olmuştur. Bununla birlikte monensin kaspaz-10 gen ekspresyonunu arttırarak apoptozu anlamlı olarak aktive etmiştir. Sunulan çalışma monensinin GBM hücrelerinin kaspaz-10 aracılı apoptoz mekanizması üzerine etkilerini gösteren ilk çalışmadır. Bizim sonuçlarımız monensinin GBM kanserinde güçlü apoptotik etkileri olan terapötik bir antikanser ilaç bileşiği olabileceğini önermektedir.

Keywords

• monensin
• U373
• apoptozis

Effects of Monensin on Caspase-10 Mediated Apoptosis in Glioblastoma Multiforme

Abstract

Glioblastoma multiforme (GBM) is the most malignant primary central nervous system tumor. Currently, there are no curative treatment options for GBM and the 5-year survival rate is less than 5%. Therefore, further studies are needed to identify effective markers and therapeutic targets for GBM treatment. Monensin is an ionophore antibiotic obtained from Streptomyces cinnamonensis with known antibacterial and antiparasitic effects. In the literature, no study has been found that shows an effect of monensin on the apoptosis mechanism of GBM cells. The aim of the present study was to investigate the effects of monensin on apoptosis-mediated cell proliferation in U373 GBM cells. The effects of monensin on U373 cell viability were investigated by XTT and its effects on apoptosis were investigated by RT-PCR and Annexin V. The IC50 value of monensin in U373 GBM cells was 4 μM at 48 hours. Monensin caused a 6-fold increase in the rate of apoptosis in U373 GBM cells. Monensin also significantly triggered apoptosis by increasing caspase-10 gene expression. The present study is the first to demonstrate the effects of monensin on the caspase-10-mediated apoptosis mechanism of GBM cells. Our results suggest that monensin may be a therapeutic anticancer drug compound with potent apoptotic effects in GBM cancer.

Keywords

• monensin
• U373
• apoptosis

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