Ginsenosides as epigenetic modulators: HDAC, DNMT, and miRNA-targeted mechanisms in tumour suppression.

Panax ginseng contains bioactive compounds called ginsenosides, which have become the subject of many studies investigating their anticancer actions. Ginsenosides act by modulating epigenetic processes, as aberrant functioning of the epigenome through abnormal methylation of DNA, modification of histones or expression of miRNA represents an important mechanism regulating the initiation and progression of cancer. Specifically, ginsenosides act through pathological pathways to inhibit tumor development by acting on the key regulators of epigenetic processes, such as HDACs or DNMTs, to restore normal expression of genes in cancer cells. Ginsenosides such as Rg3, Rh2, and compound K inhibit the activity of HDACs, thereby increasing acetylation of histones and promoting re-expression of tumor suppressor genes via this mechanism. In addition, ginsenosides regulate the activities of DNMTs, promoting the demethylation of the hypermethylated promoter regions, thereby reactivating genes that would otherwise remain silenced. Ginsenosides also modulate cancer-associated miRNA profiles, influencing cellular signaling pathways involved in proliferation, apoptosis, metastasis, and angiogenesis. Thus, through the regulation of miRNA networks, ginsenosides inhibit oncogenic signaling pathways and re-establish cellular homeostasis. In summary, ginsenosides provide an epigenetically multi-targeted strategy for treating cancer and provide a means of inhibiting tumor formation with fewer side effects than traditional chemotherapy. Thus, ongoing studies (preclinical and clinical) are needed to understand the mechanisms by which ginsenosides provide their anticancer action and to further define their clinical utility in cancer treatment.