Molecular links between metabolome and epigenome: AMPK-TET2 signalling pathway and their natural activators

Emerging evidence suggests that sustained diabetes-associated factors such as inflammation, hyperinsulinemia, and hyperglycemia are major contributors to aberrant cell proliferation and subsequent neoplastic transformation. Epidemiological studies have also highlighted that diabetes promoting a sedentary lifestyle, with or without the direct involvement of insulin, is frequently linked to cancer. However, our knowledge regarding the molecular mechanisms that correlate hyperglycemia to oncogenic transformations remains limited. In this regard, a recent study has proved that hyperglycemia inactivates AMPK, destabilizing the TET2 and its tumour-suppressive role and ultimately predisposing diabetes mellitus patients to cancer. We must explore a reverse pharmacology-based ethnopharmacological approach to managing hyperglycemia associated with oncogenesis. Botanical-derived natural products have greater structural and functional diversity with fewer or no side effects on humans. The present review discusses the molecular relationship between hyperglycemia and cancer progression and the impact of natural products as therapeutic agents on the hyperglycemia-cancer-associated signaling pathway.