Myricetinin LNCaP Androjen Bağımlı Prostat Kanseri Hücreleri Üzerine Etkisinin Araştırılması

Abstract

Prostat kanseri dünyada erkekler arasında en sık görülen ikinci kanser türüdür. Prostat kanserinin morbidite ve mortalitesi son zamanlarda artmıştır. Tedavisi için birçok alternatif yaklaşımlar geliştirilmeye çalışılsa da, prostat kanseri hala kötü prognoz sergilemekte ve yüksek ölüm oranları ile karşılaşılmaktadır. Myricetin, antikanser özelliği ile ilgi çeken doğal bir flavonoid bileşiktir. Yapılan in vitro ve in vivo çalışmalar myricetinin çeşitli mekanizmalar yoluyla prostat kanserini etkili bir şekilde inhibe ettiğini göstermektedir. Bu çalışmanın amacı artan dozlarda myricetin uygulamasının androjen reseptör bağımlı insan prostat kanser hücre hattı olan LNCaP hücrelerinin canlılığı üzerindeki etkilerini belirlemek ve apoptozla ilişkili BAX ve BCL2 genlerinin ekspresyon seviyelerini tespit etmektir. LNCaP hücreleri myricetinin 10 μM, 25 μM, 50 μM, 100 μM, 150 μM’lık konsantrasyonları ile 24 ve 48 saat süresince inkübe edilmiş ve hücre canlılığındaki değişimler 2,3-bis-(2-metoksi-4-nitro-5-sulfofenil)-2Htetrazolyum-5-karboksanilid (XTT) yöntemiyle belirlenerek IC50 değerleri hesaplanmıştır. BAX ve BCL2 gen ifadelerindeki değişimler ise Real-Time PCR metoduyla belirlenmiş ve elde edilen verilerin analizinde ΔΔCT metodu kullanılmıştır. Myricetinin uygulanan bütün dozlarda kontrole göre LNCaP hücre canlılığını azalttığı gösterilmiş olup IC50 değeri 24. saat için 123.76 μM, 48. saat için ise 84.79 μM olarak tespit edilmiştir. Ayrıca, myricetin uygulamasının apoptoz ilişkili BAX gen ifadesini istatistiksel olarak anlamlı bir düzeyde artırırken BCL2 gen ifadesini ise azalttığı görülmüştür. Myricetinin LNCaP hücrelerindeki antiproliferatif ve apoptotik etkileri daha detaylı olarak araştırılmalıdır.

Keywords

• Myricetin
• LNCaP hücre hattı
• Apoptoz
• BAX ve BCL2 Gen Ekspresyonu

Investigation of the Effect of Myricetin On Human Androgen Dependent Prostate Cancer Cells

Abstract

Prostate cancer is the second most common type of cancer amongst men worldwide. The morbidity and mortality of prostate cancer has increased recently. Although many alternative approaches have been tried to be developed for the treatment, prostate cancer still has a poor prognosis and high mortality rates. Myricetin is a natural flavonoid compound of interest for its anticancer properties. In vitro and in vivo studies show that myricetin effectively impedes prostate cancer through several mechanisms. The aim of this study was to determine the effects of increasing doses of myricetin on the viability of LNCaP cells, an androgen receptor-dependent human prostate cancer cell line, and to determine the expression levels of the apoptosis-related BAX and BCL2 genes. LNCaP cells were incubated with myricetin at concentrations of 10 μM, 25 μM, 50 μM, 100 μM, 150 μM for 24 and 48 hours and alterations in cell viability were determined by 2,3-bis-(2-methoxy-4-nitro-5-sulfophenyl) )-2Htetrazolium-5-carboxanilide (XTT) method and IC50 values were calculated. Changes in BAX and BCL2 gene expressions were investigated by Real-Time PCR and the data was analysed using ΔΔCT method. It was shown that myricetin decreased LNCaP cell viability at all doses used compared to the control, and the IC50 value was determined as 123.76 μM for the 24th hour and 84.79 μM for the 48th hour. In addition, it was observed that myricetin administration increased apoptosis associated BAX gene expression at a statistically significant level, while it was decreasing BCL2 gene expression. The antiproliferative and apoptotic effects of myricetin on LNCaP cells need to be investigated in more detail.

Keywords

• Myricetin
• LNCaP cell line
• Apoptosis
• BAX and BCL2 Gene Expressions

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