Natural compounds as epigenetic modulators: Reversing DNA hypermethylation in cancer (Review)

The development of cancer involves an intricate mechanism, including oncogene activation and tumor suppressor gene inactivation, often driven by epigenetic alterations. Notably, these epigenetic modifications, such as DNA hypermethylation, are dynamic and reversible, and emerging research suggests that dietary factors can influence them. Recent findings have examined the intricate associations between dietary compounds and cancer development, with a particular focus on the mechanisms through which natural components affect epigenetic alterations. Natural compounds have gained significant attention for their potential in chemoprevention and treatment due to their capacity to modulate DNA methylation patterns, particularly at promoter CpG islands. Chemotherapy and radiation therapy are effective cancer treatments and are often associated with severe adverse effects. As a result, there is increasing interest in exploring natural substances as alternative therapeutic options. The present review focuses on natural compounds that can reverse hypermethylation, providing a potentially safer approach for targeted cancer treatment. These bioactive agents, abundant in natural compounds, exhibit the potential to combat cancer by inhibiting metastasis, inducing cell cycle arrest and reversing DNA hypermethylation. The present review aimed to provide further in‑depth mechanistic insight into the mechanisms through which natural compounds, such as genistein, resveratrol, quercetin and capsaicin modulate DNA hypermethylation in various types of cancer, including breast, cervical, prostate and neuroblastoma. By combining <em>in silico</em>, <em>in vitro</em> and <em>in vivo</em> approaches, it uniquely integrates computational and experimental evidence to demonstrate compound‑specific reversal of epigenetic marks.