Curcumin: biochemistry, pharmacology, advanced drug delivery systems, and its epigenetic role in combating cancer

Curcumin, the principal bioactive compound of <i>Curcuma longa</i> (turmeric), has received extensive scientific attention for its remarkable pharmacological and epigenetic activities, particularly in cancer prevention and therapy. This review provides a comprehensive overview of curcumin's biochemical, pharmacological, and molecular actions. Curcumin exerts potent antioxidant, anti-inflammatory, and anticancer effects by modulating multiple signaling pathways, including NF-κB, PI3K/Akt, and Wnt/<i>β</i>-catenin. Despite its broad therapeutic potential, curcumin's clinical application is limited by poor solubility, rapid metabolism, and low systemic bioavailability. To address these challenges, advanced nanotechnology-based drug delivery systems such as nanoparticles, liposomes, micelles, and polymeric carriers have been developed to enhance its solubility, stability, and targeted bioavailability. Importantly, curcumin demonstrates a multifaceted epigenetic influence that encompasses the inhibition of DNA methyltransferases leading to DNA demethylation and reactivation of silenced tumor-suppressor genes, modulation of histone acetylation and methylation balance to restore normal chromatin accessibility, regulation of non-coding RNAs such as microRNAs, lncRNAs, and circRNAs that control gene expression, and alteration of RNA methylation (m⁶A modification) through modulation of METTL3, FTO, and YTHDF proteins, which influence mRNA stability and translation efficiency. Collectively, these molecular and epigenetic effects reinforce curcumin's potential as a promising multi-target agent for cancer prevention and therapy. Further pharmacogenomic and clinical studies are essential to standardize curcumin formulations and translate these preclinical findings into effective therapeutic applications.