Sitokalasin B Tedavisi, Nrf2 Sinyal Yoluyla U87 Glioblastoma Hücrelerinde Anti-Proliferatif Etkiler Gösterdi

Yıl 2022, Cilt: 9 Sayı: 1, 92 - 98, 31.03.2022

Ceyhan Hacıoğlu , Fatih Kar

https://doi.org/10.34087/cbusbed.993773

Öz

Giriş ve Amaç: Glioblastoma kötü prognozlu agrasif beyin tümörlerinden biridir ve glioblastoma için mevcut tedavi yöntemleri oldukça sınırlıdır. Sitokalasin B'nin (CB) kanser hücre hatları üzerinde inhibitör etki göstermektedir, ancak antikanser etkileri henüz tam olarak anlaşılamamıştır. Bu çalışmada, CB'nin U87 insan glioblastoma hücrelerinde nükleer faktör eritroid 2 ile ilişkili faktör (Nrf2) sinyal yolağı üzerinden oksidatif, antioksidan ve DNA hasar mekanizmaları üzerindeki etkisini araştırmayı hedefledik.
Gereç ve Yöntemler: İlk olarak, CB'nin U87 hücrelerindeki sitotoksik konsantrasyonlarını MTT analizi ile belirledik. Ardından, CB'nin Nrf2 seviyeleri üzerindeki etkisini ve bununla bağlantılı olarak total oksidan kapasite (TOS), malondialdehit (MDA), süperoksit dismutaz (SOD) ve glutatyon peroksidaz (GPx) seviyeleri ölçüldü. Son olarak, CB ile tedavi edilen U87 hücrelerindeki DNA hasarını tespit edebilmek için 8-hidroksi-2'-deoksiguanozin (8-OHdG) seviyeleri ölçüldü.
Bulgular: MTT analizine göre, CB'nin U87 hücrelerinde canlılığı konsantrasyona bağımlı bir şekilde azalttığını belirledik ve IC50 konsantrasyonunu 62,8 μM olarak tespit ettik. Ardından, 5,1, 33,6 ve 62,8 μM CB ile tedavi edilen U87 hücrelerinde TOS, MDA ve 8-OHdG seviyeleri konsantrasyon bağımlı bir şekilde artmıştır (p<0,05). Aksine, CB tedavisi U87 hücrelerindeki Nrf2, SOD ve GPx seviyeleri azalmıştır (p<0,05). CB, U87 glioblastoma hücre proliferasyonunu Nfr2 sinyal yolağı üzerinden inhibe etmiştir.
Sonuç: CB tedavisi, U87 hücrelerinde oksidatif stresi ve DNA hasarını indüklemesinin yanı sıra antioksidan enzimlerin seviyelerini azaltmıştır, bu da CB'nin glioblastoma için potansiyel terapötik ajan olabileceğini düşündürdü. Ancak, CB'nin diğer kanser hücre hatlarında ve in vivo modellerdeki etkilerini araştıran daha ileri çalışmalara ihtiyaç vardır.

Anahtar Kelimeler

Sitokalasin B, U87 Glioblastoma Hücreler, Oksidatif Stres, Antioksidan, DNA hasarı

Cytochalasin B Treatment Showed Anti-Proliferative Effects in U87 Glioblastoma Cells via Nrf2 Signaling Pathway

Öz

Objective: Glioblastoma is one of the aggressive brain tumors with a poor prognosis, and the available treatments for glioblastoma are quite limited. Cytochalasin B (CB) has an inhibitory effect on cancer cell lines, but its anticancer effects are not yet fully understood. In this study, we aimed to investigate the effect of CB on oxidative, antioxidant and DNA damage mechanisms via nuclear factor erythroid 2 associated factor (Nrf2) signaling pathway in U87 human glioblastoma cells.
Materials and Methods: Firstly, we determined the cytotoxic concentrations of CB in U87 cells by MTT analysis. Then, the effect of CB on Nrf2 levels and related total oxidant capacity(TOS), malondialdehyde (MDA), superoxide dismutase(SOD) and glutathione peroxidase(GPx) levels were measured. Finally, 8-hydroxy-2'-deoxyguanosine(8-OHdG) levels were measured to detect DNA damage in U87 cells treated with CB.
Results: According to MTT analysis, we determined that CB decreased viability in U87 cells in a concentration-dependent manner and determined the IC50 concentration to be 62.8μM. Subsequently, TOS, MDA, and 8-OHdG levels increased in a concentration-dependent manner in U87 cells treated with 5.1, 33.6, and 62.8μM CB (p<0.05). In contrast, Nrf2, SOD and GPx levels were decreased in CB-treated U87 cells (p<0.05). CB inhibited U87 glioblastoma cell proliferation via the Nfr2 signaling pathway.
Conclusion: CB induced oxidative stress and DNA damage in U87 cells, as well as reduced antioxidant enzymes levels, suggesting that CB may be a potential therapeutic agent for glioblastoma. However, further studies investigating the effects of CB in other cancer cell lines and in vivo models are needed.

Anahtar Kelimeler

Cytochalasin B, Cytochalasin B, Glioblastoma Cells, Oxidative Stress, Antioxidant, DNA damage

Kaynakça

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