Oksidatif, Apoptotik ve İnflamatuar Sinyal Yolakları üzerinden C6 Glioblastoma Hücrelerindeki ML351'in Antiproliferatif Etkileri

Yıl 2022, , 36 - 42, 14.01.2022

Ceyhan Hacıoğlu Fatih Kar

https://doi.org/10.33631/sabd.1055238

Öz

Amaç: Kanser tedavisindeki başarılı yaklaşımlardan biri de spesifik inhibitörlerin kullanılmasıdır. Çoklu doymamış yağ asitlerinin metabolizmasından sorumlu olan 12/15-lipoksijenaz (12/15-LOX) nöronlarda oksidatif stres kaynaklanan hücre ölümüne aracılık etmesinin yanı sıra, kanser gibi birçok önemli hastalıkta yer alan metabolitlerin üretemini de gerçekleştirir. Bu çalışmada, 12/15-LOX inhibitörü olan ML351'in C6 glioblastoma hücrelerin üzerindeki anti-proliferatif etkilerini çeşitli biyokimyasal süreçler üzerinden araştırılması amaçlanmıştır.
Gereç ve Yöntemler: Çalışmada önce C6 hücreleri için sitotoksik ML351 konsantrasyonları metil tiazolil tetrazolyum (MTT) kullanılarak tespit edilmiştir ve ardından total oksidan kapasite (TOS), sitokrom c (CYC), kaspaz 3 (CASP3), tümör nekroz faktör alfa (TNF-α) ve interlökin-6 (IL-6) seviyeleri ölçüldü.
Bulgular: Sonuç olarak, ML351 C6 hücreleri üzerinde konsantrasyon bağımlı anti-proliferatif etkilerinin olduğu görüldü. ML351 uygulamasının C6 hücrelerinde oksidatif strese neden olarak TOS seviyelerini artırdığı belirlendi. ML351 uygulanması kontrol grubu ile karşılaştırıldığında CASP3 ve CYC seviyelerini artırdı (p<0,001). Bu sonuçlara göre, ML351 uygulamasının C6 hücrelerinde apoptozu indüklediği görüldü. Öte yandan, ML351 ile tedavi edilen C6 hücrelerinde kontrol grubuna göre TNF-α ve IL-6 seviyelerinin düştüğü belirlendi (p<0,01).
Sonuç: Çalışmamız, C6 glioma hücrelerinde ML 351 uygulamasının pro-oksidan/oksidan dengesini bozarak oksidatif hasar ve apoptoza neden olduğunu ve inflamasyonu azalttığını göstermektedir. Bu nedenle bir antikanser ilaç olma potansiyeline sahip ML351'in farklı kanser hücre hatlarındaki faklı metabolik yolaklar üzerindeki etkilerini araştıran daha ileri çalışmalar yapılmalıdır.

Anahtar Kelimeler

ML351, C6glioblastoma, oksidatif stres, apoptoz, inflamasyon

Antiproliferative Effects of ML351 on C6 Glioblastoma Cells through Oxidative, Apoptotic and İnflammatory Signaling Pathways

Öz

Aim: One of the successful approaches in cancer treatment is the use of specific inhibitors. Responsible for the metabolism of polyunsaturated fatty acids, 12/15-lipoxygenase (12/15-LOX) not only mediates cell death caused by oxidative stress in neurons, but also produces metabolites involved in many important diseases such as cancer. In this study, it was aimed to investigate the anti-proliferative effects of ML351, 12/15-LOX inhibitor, on C6 glioblastoma cells through various biochemical processes.
Material and Methods: In the study, cytotoxic ML351 concentrations for C6 cells were determined using methyl thiazolyl tetrazolium (MTT), and then total oxidant capacity (TOS), cytochrome c (CYC), caspase 3 (CASP3), tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6) levels were measured.
Results: As a result, it was found to have concentration dependent anti-proliferative effects on ML351 C6 cells. It was determined that ML351 treatment increased TOS levels by causing oxidative stress in C6 cells. The ML351 treatment increased CASP3 and CYC levels compared to the control group (p<0.01). Based on these results, it was observed that ML351 treatment induced apoptosis in C6 cells. On the other hand, TNF-α and IL-6 levels were decreased in C6 cells treated with ML351 compared to the control group (p<0.01).
Conclusion: Our study shows that ML 351 treatment causes oxidative damage and apoptosis by disrupting the pro-oxidant/oxidant balance and decreases inflammation in C6 glioma cells. Therefore, further studies should be conducted to investigate the effects of ML351, which has the potential to be an anticancer drug, on different metabolic pathways in different cancer cell lines.

Anahtar Kelimeler

ML351, C6 glioblastoma, oxidative stress, apoptosis, inflammation

Kaynakça

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