Metastatik Prostat Kanserinde Nobiletinin Sitotoksik ve Apoptotik Etkisinin Belirlenmesi

Abstract

Amaç: Nobiletin, C₂₁H₂₂O₈ kimyasal formülü ve 402.39 kD molekül ağırlığına sahip, turunçgil kabuklarında bulunan bir O-metillenmiş flavanoiddir. Nobiletinin sahip olduğu antikanser, antiviral ve anti-inflamatuar etkilerden dolayı, kanser tedavisinde potansiyel terapötik bir ajan olarak dikkat çekmektedir. Prostat kanserinde metastaza neden olan kanser hücrelerinin invaziv özelliğinin yüksek olması, hastalığın tedavisini zorlaştırmakta ve hastalarda kötü prognoza neden olan en önemli faktörlerden birisidir. Bu nedenle mevcut çalışmada, nobiletinin yüksek metastatik potansiyeli olan insan prostat kanseri (PC-3) ve insan göbek kordonu veni endotel hücrelerinde  (HUVEC) sitotoksik ve apoptotik etkilerinin belirlenmesi amaçlanmıştır.

Gereç ve Yöntemler: Mevcut çalışmada, PC-3 ve HUVEC hücrelerinde nobiletinin sitotoksik etkisi WST-1 analizi ile, apoptotik etkisi ise Annexin V, akridin oranj boyaması ve hücre siklusu analizleri ile kalitatif ve kantitatif olarak belirlenmiştir.

Bulgular: WST-1 analizi ile elde edilen bulgulara göre, 24 ve 48 saat boyunca farklı konsantrasyonlarda nobiletin uygulanan PC-3 hücrelerinde canlılık oranının anlamlı bir şekilde azaldığı belirlenmiştir. Annexin V ve hücre siklusu analizleri ile elde edilen verilere göre, nobiletinin PC-3 hücrelerinde özellikle erken apoptoza ve G0/G1 fazında artışa neden olduğu belirlenmiştir. Ayrıca, HUVEC hücrelerinde 80 µM konsantrasyona kadar toksik etkisinin olmadığı belirlenmiştir.

Sonuç: Kontrol hücreleri ile karşılaştırmalı olarak nobiletinin metastatik prostat kanseri hücrelerinde anti-proliferatif etkisinin, erken apoptoz ve G0/G1 fazında hücre miktarında artış ile gerçekleştiği gösterilmiştir. Ancak, nobiletinin metastatik prostat kanserinde neden olduğu apoptotik ölümün moleküler mekanizmasının in vitro ve in vivo olarak detaylı araştırılması gerekmektedir.

Keywords

• Prostat kanseri,Flavonoidler,Nobiletin,Apoptoz

References

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