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

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 <em>Curcuma longa</em>, 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 <em>BRCA1.</em> 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&nbsp;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.