Assessment of In Vitro Cytotoxic Efficacy of Atypical Antidepressant Bupropion Hydrochloride in Glioma

Öz

Bupropion hydrochloride (Wellbutrin; WB), an atypical antidepressant of the aminoketone class, is a selective norepinephrine and dopamine reuptake inhibitor used in the treatment of major depression. In this study, the potential effects of bupropion on brain cancer were investigated using rat C6 glioma cells. The cytotoxicity levels and IC50 values of bupropion were determined using the MTT method. Also, we analyzed caspase-3 immunoreactivity with immunofluorescence staining. Additionally, the effectiveness of the determined bupropion IC50 dose on colony development was assessed using a colony formation assay. It was found that bupropion had toxic activity on glioma cancer cells in direct proportion to the increase in applied doses. As a result of the immunocytochemical analysis performed on cells with IC50 value, it was found that the drug at the IC50 dose increased caspase-3 immunoreactivity in C6 cells compared to the control group. In addition, a decrease in the number of colonies was detected. Considering that bupropion increased apoptotic caspase-3 activation in C6 cells at the IC50 dose, elucidation of the molecular mechanisms behind these effects may contribute to the development of a new perspective in treatment.

Anahtar Kelimeler

• Brain cancer
• C6 cell
• Caspase-3
• Immunofluorescence
• anticancer

Glioma Hücrelerinde Atipik Antidepresan Bupropion Hidroklorürün in Vitro Sitotoksik Etkinliğinin Değerlendirilmesi

Öz

Aminoketon sınıfından atipik bir antidepresan olan bupropion hidroklorür (Wellbutrin; WB), majör depresyon tedavisinde kullanılan seçici bir norepinefrin ve dopamin geri alım inhibitörüdür. Bu çalışmada, bupropionun beyin kanseri üzerindeki potansiyel etkileri rat C6 glioma hücreleri kullanılarak araştırılmıştır. Bupropionun sitotoksisite düzeyleri ve IC50 değerleri MTT yöntemi kullanılarak belirlenmiştir. Ayrıca, immünfloresan boyama ile kaspaz-3 immünoreaktivitesi analiz edilmiştir. Belirlenen bupropion IC50 dozunun koloni oluşturma üzerindeki etkinliğini tespit etmek için koloni oluşumu deneyi gerçekleştirilmiştir. Bupropionun uygulanan dozlardaki artışla doğru orantılı olarak glioma kanser hücreleri üzerinde toksik aktiviteye sahip olduğu bulunmuştur. IC50 değerinde bupropion uygulanan hücrelerde yapılan immünositokimyasal analiz sonucunda, ilacın IC50 dozunda C6 hücrelerinde kontrol grubuna kıyasla kaspaz-3 immünoreaktivitesini artırdığı bulunmuştur. Ayrıca koloni sayısında azalma tespit edilmiştir. Bupropionun IC50 dozunda C6 hücrelerinde apoptotik kaspaz-3 aktivasyonunu artırdığı göz önüne alındığında, bu etkilerin ardındaki moleküler mekanizmaların aydınlatılması, tedavide yeni bir bakış açısı geliştirilmesine katkı sağlayabilir.

Anahtar Kelimeler

• Beyin kanseri
• C6 hücresi
• Kaspaz-3
• İmmunfloresan
• Antikanser

Kaynakça

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