Vitaminlerin Kanserdeki Rolü: Etki Mekanizmaları
Özet
Kanser, protoonkogenler, tümör baskılayıcı genler ve DNA tamir genlerinde meydana gelen mutasyonlar sonucu gelişen, karsinogenez süreçleriyle ilerleyen ve dünyada sıklığı giderek artan önemli bir halk sağlığı sorunudur. Beslenmeyle alınan vitaminler, karsinogenezin farklı evrelerinde hücresel ve moleküler düzeydeki etki mekanizmaları aracılığıyla kanserin önlenmesi ve tedavisinde dikkat çekici potansiyeller sunmaktadır. A vitamini ve retinoidler, RAR ve RXR nükleer reseptörleri üzerinden hücresel proliferasyonu, apoptozu ve farklılaşmayı düzenlemekte; akut promyelositik lösemi ve premalign lezyonlarda belirgin terapötik faydalar sağlamaktadır. Folat, B2, B6 ve B12 gibi B grubu vitaminleri, tek karbon metabolizması ve S-adenosilmetiyonin döngüsü üzerinden DNA metilasyonu, sentezi ve stabilitesinde anahtar roller üstlenmekte; yetersizliklerinde urasilin DNA'ya hatalı katılımı ve p53 geni mutasyonları gibi genomik kararsızlıklar yaşanabilmektedir. D vitamini, VDR reseptör etkileşimi ile E-kadherin ekspresyonunu indükleyip VEGF supresyonu sağlayarak tümör invazyonu ile anjiyogenezi baskılamakta, ayrıca AMPK-mTOR-TXNIP sinyal eksenini düzenlemektedir. C ve E vitaminleri ise serbest radikalleri nötralize eden antioksidan savunma mekanizmalarının yanı sıra, yüksek dozlarda reaktif oksijen türevleri üreterek kanser hücrelerine özgü prooksidan sitotoksisite ve PKC inhibisyonu yoluyla apoptozu indükleyebilmektedir. Tüm bu bulgular, vitaminlerin ve mikro besinlerin karsinogenezdeki belirleyici rolünü ortaya koymakla birlikte etki mekanizmalarının ve klinik uygulama dozlarının netleştirilmesi için daha fazla çalışmaya gereksinim duyulduğunu göstermektedir.
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