Glioblastomada melatoninin hücresel düzeyde antiepileptik etkisinin incelenmesi
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Date
2023
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Tekirdağ Namık Kemal Üniversitesi
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info:eu-repo/semantics/openAccess
Abstract
Nöbetler primer beyin tümörlerinin iyi bilinen bir semptomudur ve antikonvulzan kullanımı oldukça yaygındır. Glioblastoma ve tümörle ilişkili epilepsi santral sinir sistemindeki ana eksitatör nörotransmitter olan glutamatın oynadığı kritik rol ve birkaç patofizyolojik mekanizma ile birbiriyle yakından ilişkilidir. Glutamat, sistein/glutamat antiporter çözünen taşıyıcı ailesi 7 üye 11 (SLC7A11) yoluyla glioblastoma hücreleri tarafından salınır. Glioblastoma hücrelerinde SLC7A11 ekspresyonu artışı ile birlikte nöbet ilişkisinin olduğu bildirilmektedir. Melatoninin ise antioksidan, antieksitotoksik, antineoplastik ve antiinflamatuar etkilerinin olduğu gösterilmiştir. Epilepside antiepileptik özellik gösterebileceği düşünülmektedir. Nöbetle birlikteliği oldukça sık görülen glioblastomada melatoninin antikonvulzan etkisine dair literatürde çalışma izlenmemiş olup bu çalışmada in vitro olarak glioblastoma hücre hattına melatonin uygulaması sonucunda hücre canlılığına ve glioblastomada nöbet aktivitesiyle ilişkili olan SLC7A11 proteini üzerine etkisi incelenmiştir. Tümör olmayan hücrelerdeki etkisiyle kıyaslamak amacıyla astrosit hücre hattı kullanılmıştır. Hücre canlılığına etkisi koloni sağkalım deneyleri ile değerlendirilmiştir. Melatoninin glutamaterjik yolaktaki etkisi ise Western Blot yönteminde SLC7A11 proteini çalışılarak incelenmiştir. 24, 48 ve 72 saat 10-3, 10-4, 10-5, 10-6, 10-7 M melatonin uygulanan hücre gruplarında, 72 saat 10-3 M melatonin uygulamasının glioblastoma hücrelerinde sağkalımı %50'den fazla azalttığı saptanmıştır. Glioblastoma ve astrosit hücrelerinde melatonin uygulaması ile SLC7A11 proteinininde Western Blot analizi sonucunda kontrole göre azalma izlenmemiştir. Glioblastomada melatoninin süre ve konsantrasyona bağımlı olarak hücre sağkalımına etki etmesi antineoplastik etkisini desteklemektedir. Melatoninin glioblastoma hücrelerinde, glutamat ve ferroptoz mekanizmasında yer alan SLC7A11 proteini üzerine olan etkisinin ise ilk kez bu çalışma ile incelenmesi gelecek çalışmalar için yol gösterici olacaktır. Anahtar kelimeler: Glioblastoma, Epilepsi, SLC7A11 proteini, Melatonin
Seizures are a well-known symptom of primary brain tumors and the use of anticonvulsants is quite common. Glioblastoma and tumor-associated epilepsy are closely related each other due to the critical role played by glutamate, the main excitatory neurotransmitter in the central nervous system, and several pathophysiological mechanisms. Glutamate is released by glioblastoma cells via the cysteine/glutamate antiporter soluble transporter family 7 member 11 (SLC7A11). It has been reported that there is an association with seizures and increased SLC7A11 expression in glioblastoma cells. Melatonin has been shown to have antioxidant, antiexcitotoxic, antineoplastic and anti-inflammatory effects. It is thought that it may have antiepileptic properties in epilepsy. There is no study in the literature on the anticonvulsant effect of melatonin in glioblastoma, which is frequently associated with seizures. In this study, the effect of melatonin treatment on cell viability and SLC7A11 protein in glioblastoma cells in vitro was examined. An astrocyte cell line was used to compare its effect on non-tumor cells. Its effect on cell viability was evaluated by colony formation assay. The effect of melatonin on the glutamatergic pathway was examined by studying the SLC7A11 protein in the Western Blot method. In groups treatment to melatonin which 10-3, 10-4, 10-5, 10-6, 10-7 M for 24, 48 and 72 hours, it was determined that melatonin 10-3 M for 72 hours exerted reduced the survival of glioblastoma cells by more than 50%. As a result of Western Blot analysis in glioblastoma and astrocyte cells with treated with melatonin, no decrease was observed in SLC7A11 protein compared to the control. We have seen that melatonin affects cell survival in glioblastoma in a time- and concentration-dependent manner supports its antineoplastic effect. The fact that this study shows for the first time the effect of melatonin on the SLC7A11 protein, which is involved in the glutamate and ferroptosis mechanisms in glioblastoma cells, will be a guide for future studies. Keywords: Glioblastoma, Epilepsy, SLC7A11 protein, Melatonin
Seizures are a well-known symptom of primary brain tumors and the use of anticonvulsants is quite common. Glioblastoma and tumor-associated epilepsy are closely related each other due to the critical role played by glutamate, the main excitatory neurotransmitter in the central nervous system, and several pathophysiological mechanisms. Glutamate is released by glioblastoma cells via the cysteine/glutamate antiporter soluble transporter family 7 member 11 (SLC7A11). It has been reported that there is an association with seizures and increased SLC7A11 expression in glioblastoma cells. Melatonin has been shown to have antioxidant, antiexcitotoxic, antineoplastic and anti-inflammatory effects. It is thought that it may have antiepileptic properties in epilepsy. There is no study in the literature on the anticonvulsant effect of melatonin in glioblastoma, which is frequently associated with seizures. In this study, the effect of melatonin treatment on cell viability and SLC7A11 protein in glioblastoma cells in vitro was examined. An astrocyte cell line was used to compare its effect on non-tumor cells. Its effect on cell viability was evaluated by colony formation assay. The effect of melatonin on the glutamatergic pathway was examined by studying the SLC7A11 protein in the Western Blot method. In groups treatment to melatonin which 10-3, 10-4, 10-5, 10-6, 10-7 M for 24, 48 and 72 hours, it was determined that melatonin 10-3 M for 72 hours exerted reduced the survival of glioblastoma cells by more than 50%. As a result of Western Blot analysis in glioblastoma and astrocyte cells with treated with melatonin, no decrease was observed in SLC7A11 protein compared to the control. We have seen that melatonin affects cell survival in glioblastoma in a time- and concentration-dependent manner supports its antineoplastic effect. The fact that this study shows for the first time the effect of melatonin on the SLC7A11 protein, which is involved in the glutamate and ferroptosis mechanisms in glioblastoma cells, will be a guide for future studies. Keywords: Glioblastoma, Epilepsy, SLC7A11 protein, Melatonin
Description
Tıp Fakültesi, Nöroloji Ana Bilim Dalı
Keywords
Nöroloji, Neurology
