Research progress on active components from natural medicines inhibiting tumor via epigenetic regulation.
Tumor is a major disease that seriously threatens human health, and its occurrence and progression involve complex interactions between the genome, epigenome, and environmental factors. Epigenetic modifications-such as DNA methylation, histone modifications, non-coding RNA regulation, and mRNA modifications-play key roles in tumor progression, metastasis, and drug resistance. Natural medicines offer multi-target and holistic regulatory effects, showing unique advantages in cancer therapy. Emerging evidence suggests that natural medicines and its active components can exert anti-tumor activities by modulating epigenetic mechanisms. This review summarizes natural medicines-mediated epigenetic regulation against tumors. It details how natural medicines influences DNA methylation by suppressing DNA methyltransferases (DNMTs) and altering tumor suppressor gene promoter methylation. The modulation of histone modifications through targeting histone deacetylases (HDACs), histone lysine methyltransferases (HKMTs), and histone lysine demethylases (HKDMs) is also discussed. Furthermore, the review covers natural medicines's regulation of non-coding RNAs (e.g., lncRNAs, miRNAs, circRNAs) and their downstream pathways, as well as its role in mRNA modifications, notably N6-methyladenosine (m6A). Overall, this work highlights the epigenetic potential of natural medicines in tumor therapy, enhancing the mechanistic understanding of its anti-tumor effects and supporting natural medicines modernization and precision oncology. However, challenges remain due to natural medicines complexity and tumor epigenetic heterogeneity, calling for deeper investigation and clinical validation.