OVER KANSERİNDE KURKUMİN İLE EPİGENETİK DÜZENLEME: miRNA AĞLARI, HISTON MODİFİKASYONLARI VE DNA METİLASYONU ÜZERİNE BİR İNCELEME

Öz

Over kanseri, geç evrede teşhis edilmesi, yüksek metastaz potansiyeli ve genellikle gelişen kemoterapi direnci nedeniyle, jinekolojik kanserlerden kaynaklanan ölümlerin başlıca nedenlerinden biri olmaya devam etmektedir. Mevcut tedavi yaklaşımları, tümör ilerlemesinin altında yatan karmaşık mekanizmaları yeterince ele alamamakta ve bu durum yenilikçi stratejilere olan ihtiyacı ortaya koymaktadır. Zerdeçalın (Curcuma longa) biyoaktif bir polifenolü olan kurkumin, çok yönlü anti-kanser özellikleri ile güçlü bir epigenetik düzenleyici olarak öne çıkmıştır. Bu derlemede, kurkuminin over kanseri patogenezinde önemli rol oynayan mikroRNA (miRNA/ miR) düzenlemesi, histon modifikasyonları ve DNA metilasyonu gibi temel epigenetik mekanizmaları nasıl modüle ettiğine dikkat çekilmektedir. Kurkumin, tümör baskılayıcı miRNA'ları yukarı regüle ederken, onkojenik miRNA'ları aşağı regüle ederek miRNA ağlarını seçici şekilde yeniden programlamaktadır. Bu sayede, epitelmezenkimal dönüşümü ve kemoterapi direncini azaltabilmektedir. Ayrıca, kurkumin, histon deasetilazları (HDAC'ler) ve EZH2 aracılı histon metilasyonunu inhibe ederek, BRCA1 gibi kritik tümör baskılayıcı genlerin yeniden aktivasyonunu sağlamaktadır. DNA metiltransferaz (DNMT) aktivitesini baskılayarak, promotör hipermetilasyonunu tersine çevirmekte ve tümör baskılayıcı gen ekspresyonunu artırmaktadır. Kurkuminden kaynaklanan bu sinerjik epigenetik düzenlemeler, onkojenik yolları engellemekte, kemoterapi duyarlılığını artırmakta ve tümör hücrelerinin bağışıklık sistemi tarafından tanınmasını sağlamaktadır. Ancak, kurkuminin terapötik potansiyeli düşük biyoyararlanımı nedeniyle sınırlıdır; bu durum, nanopartiküller ve lipozomlar gibi yenilikçi formülasyonlarla aşılmaya çalışılmaktadır. İlaç dağıtım sistemlerinin optimize edilmesi, uzun vadeli epigenetik etkilerin daha iyi anlaşılması ve klinik çalışmalarla terapötik etkinliğin doğrulanması için daha fazla araştırmaya ihtiyaç vardır. Bu derleme, kurkuminin tümör progresyonu ve direncinde rol oynayan kritik epigenetik mekanizmaları inceleyerek, over kanseri tedavisine katkı sağlama potansiyelini vurgulamaktadır.

Anahtar Kelimeler

• Over kanseri
• kurkumin
• epigenetik

EPIGENETIC REGULATION BY CURCUMIN IN OVARIAN CANCER: A FOCUS ON miRNA NETWORKS, HISTONE MODIFICATIONS AND DNA METHYLATION

Öz

Ovarian cancer remains a leading cause of gynaecological cancerrelated deaths, driven by its late-stage diagnosis, high metastatic potential, and frequent development of chemoresistance. Current therapeutic strategies often fail to address the intricate mechanisms underlying tumour progression, necessitating innovative approaches. Curcumin, a bioactive polyphenol derived from Curcuma longa, has emerged as a potent epigenetic regulator with multifaceted anticancer properties. This review highlights curcumin’s ability to modulate key epigenetic mechanisms such as microRNA (miRNA/miR) regulation, histone modifications, and DNA methylation, which are central to ovarian cancer pathogenesis. Curcumin selectively reprograms miRNA networks, restoring tumour-suppressive miRNAs while downregulating oncogenic miRNAs, thereby mitigating epithelial-mesenchymal transition and chemoresistance. In addition, curcumin inhibits histone deacetylase (HDACs) and EZH2-mediated histone methylation, reactivating critical tumoursuppressor genes like BRCA1. Through its suppression of DNA methyltransferase (DNMT) activity, curcumin reverses promoter hypermethylation, further enhancing tumour-suppressor gene expression. These synergistic epigenetic modulations disrupt oncogenic pathways, improve chemotherapy sensitivity, and restore the immune recognition of tumour cells. Despite its promise, poor bioavailability limits the clinical translation of curcumin, but advanced formulations, including nanoparticles and liposomes, overcome this limitation. Further research is essential to optimise delivery systems, elucidate long-term epigenetic effects, and validate therapeutic efficacy through clinical trials. This review underscores curcumin’s potential to enhance current ovarian cancer therapies by addressing the critical epigenetic mechanisms involved in tumour progression and resistance.

Anahtar Kelimeler

• Ovarian cancer
• curcumin
• epigenetics

Kaynakça

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