Differential regulation of antioxidant enzymes by resveratrol in healthy and cancerous hepatocytes

Abstract

Üzüm, yaban mersini, ahududu, dut ve yer fıstığı gibi bitkilerde bulunan resveratrol, çeşitli patolojik sorunlara karşı koruma sağlayan doğal olarak sentezlenmiş bir polifenoldür. Kanser hücrelerinde oksidatif stresin artışı ve hücresel antioksidan sistemlerin baskılanması belirlenmiş olup, bitkisel antioksidanların çeşitli kanser türlerinin tedavisinde yardımcı madde olarak kullanılabileceği öngörülmektedir. Bu çalışmada, güçlü bir antioksidan olan resveratrolün sağlıklı ve kanserli karaciğer hücrelerinde antioksidan enzimlerin gen ekspresyonu ve aktiviteleri üzerindeki etkileri araştırılmıştır. Karaciğer kanseri hücreleri (HepG2) ve sağlıklı hepatositler (THLE2) resveratrol ile farklı dozlarda (25-, 50-, 75- µM) 48 saat süreyle muamele edildikten sonra antioksidan enzimlerin gen ekspresyon seviyeleri qRT-qPCR ile, aktiviteleri ise spektrofotometrik olarak ölçülmüştür. Sonuçlar, THLE2 hücrelerindeki tüm antioksidan enzimlerin resveratrolün tüm dozlarında baskılandığını, ancak bunun tersine HepG2 hücrelerinde antioksidan enzimlerin yukarı regülasyonunu göstermiştir. Sağlıklı hücrelerde görülen gen ekspresyonundaki azalma, katalaz ve glutatyon S-transferazın enzimatik aktivitelerinin baskılanmasıyla paralel değiştiği, ancak kanser hücresindeki aktivite değişikliklerinin anlamlı olmadığı belirlenmiştir. Sağlıklı ve kanserli hepatositlerde antioksidan enzim sistemlerinin farklı olarak düzenlemesi, kanser hücrelerinde antioksidan enzimlerin oksidatif hasara karşı koruyucu bir işlev olarak uyarılmasını gösterirken, sağlıklı hücrelerde azalmış ekspresyon, tersine antioksidan ihtiyacının azalmasına işaret etmektedir. Bu nedenle resveratrol, kanser hücrelerinde antioksidan enzimleri aktive ederek hücresel stresi azaltabilecek moleküler mekanizmaları etkileyerek kanser tedavisinde etkili olabilir.

Keywords

• Resveratrol
• antioxidant enzymes
• gene expression
• oxidative stress

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