Metastatik Prostat Kanserinde Nobiletinin Sitotoksik ve Apoptotik Etkisinin Belirlenmesi

Yıl 2018, Cilt: 8 Sayı: 4, 766 - 774, 30.12.2018

Gamze Güney Eskiler , Asuman Deveci Özkan , Süleyman Kaleli

https://doi.org/10.31832/smj.485666

Cited By: 4

Öz

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.

Anahtar Kelimeler

Prostat kanseri, Flavonoidler, Nobiletin, Apoptoz

Kaynakça

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