ÖZET
Amaç:
Glutatyon (GSH), glisin, glutamik asit ve sisteinden oluşan bir tripeptiddir. Metiyonin ve sistein gibi kükürt içeren amino asitler hücrelerde artarsa GSH seviyesi yükselmektedir. GSH vücuttaki en önemli ve güçlü antioksidanlardan biridir ve oksidatif stresi azaltmaktadır. GSH’nin azaltılması, apoptoz aktivitesini ve çoklu ilaç direnci proteinlerini (MRP’ler) etkilemektedir. Bu çalışmada, kükürt içeren glisin imin türevlerinin, MCF-7 (meme kanseri) ve DLD-1 (kolon kanseri) hücre hatlarında çoklu ilaç direnci proteinlerine (MRP’ler) ve apoptoz mekanizmasına etkisini araştırmayı amaçladık.
Yöntemler:
MCF-7 ve DLD-1 hücre hatlarında; çoklu ilaç direnci proteinleri (ABCB1, ABCC3, ABCC10, ABCC11 ve ABCG2), apoptoz mekanizması proteinleri (BAX, BACL-2, P53, PARP, CASP3), ısı şoku proteinleri (HSP’ler) ve endoplazmik retikulum (ER) GRP’ler mRNA seviyeleri qRT-PCR yöntemi ile belirlendi.
Bulgular:
Bileşikler çoklu ilaç direncinde (MDR) gen ekspresyonunu azalttı ve pro-apoptoz mekanizması genlerinde (BAX, P53, CASP3) ekspresyonu artırdı. HSP'ler, BCL-2 ve PARP gen ekspresyonları azaldı. GRP gen ekspresyonunda önemli bir azalma olmadı. Bileşiklerin, ABCC3 dışındaki çoklu ilaç direnci genleri (ABCB1, ABCC10, ABCC11 ve ABCG2) üzerinde önemli etkilere sahip olduğu gösterilmiştir. Ayrıca bileşiklerin apoptoz mekanizması genleri ve HSP’ler üzerinde önemli etkilere sahip olduğu tespit edilmiştir.
Sonuç:
Sonuçlarımız, sülfür içeren glisin imin türevlerinin, özellikle meme ve kolon kanserinde anti-kanser ajanı olabilecek önemli ve güçlü bir seçenek olabileceğini göstermektedir.
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