Kanserde Epigenetik Yaklaşımlar: Polifenollerin Terapötik Potansiyelleri
Özet
Kanser, genetik sapmaların yanı sıra DNA metilasyonu, histon modifikasyonları ve mikroRNA müdahaleleri gibi geri dönüşümlü epigenetik mekanizmaların bozulması sonucu gelişen karmaşık bir biyolojik disfonksiyondur. Kanser vakalarının %90’ı somatik mutasyonlar, diyet ve çevresel faktörlerle ilişkili olup beslenme düzeninin modifiye edilmesi ve yaşam tarzı değişiklikleriyle büyük oranda önlenebilmektedir. Günümüzde kullanılan sentetik epigenetik ilaçların (DNMT ve HDAC inhibitörleri) yüksek toksisiteye ve özgüllük eksikliğine yol açması, daha güvenli ve spesifik alternatiflerin geliştirilmesini zorunlu kılmıştır. Bu kapsamda yeşil çay, üzüm, meyve ve sebzelerde yaygın olarak bulunan EGCG, resveratrol, apigenin ve quercetin gibi diyet polifenolleri güçlü epigenetik modülatörler olarak öne çıkmaktadır. Polifenoller, DNA metiltransferaz (DNMT) ve histon deasetilaz (HDAC) enzim aktivitelerini inhibe ederek metilasyon nedeniyle susturulmuş tümör süpresör genleri yeniden aktive etmekte, apoptozu tetiklemekte ve miR-16 ile miR-217 gibi mikroRNA ekspresyon seviyelerini düzenlemektedir. Ayrıca kanser hücrelerini kemoterapötik ajanlara karşı daha duyarlı hale getirerek karsinojenik süreçleri durdurma veya tersine çevirme potansiyeli sergilemektedirler. Besin maddeleriyle alınan bu fitokimyasallar "epigenetik diyet" kavramını doğurmuş olup kanser kemoprevensiyonu ve tedavisinde toksik olmayan, klinik açıdan son derece vaat edici yenilikçi terapötik yaklaşımlar sunmaktadır.
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