Telomeres and Telomerase: Targets for Chemoprevention of Hepatocellular Carcinoma With Bioactive Food Compounds

ABSTRACT The maintenance of telomere length by telomerase plays an essential role in senescence, aging, and cancer. Mutations in the TERT promoter, a telomerase subunit, are frequent in human cancers. In hepatocellular carcinoma (HCC), telomere shortening contributes to preneoplastic conditions such as cirrhosis. Telomerase activation during cirrhosis may reduce chromosomal instability, while its suppression in early dysplastic nodules may prevent hepatocarcinogenesis. Evidence suggests that bioactive food compounds (BFCs) can reduce the incidence and/or delay the onset of HCC by modulating telomerase activity. A systematic review was conducted on the role of BFCs in telomerase activity during hepatocarcinogenesis. BFCs were analyzed in isolated form or as part of extracts and categorized into fatty acids, isoprenoids, isothiocyanates, and phenolic compounds. Despite structural diversity, BFCs modulate telomerase through common mechanisms, including inhibition of activating proteins at the TERT promoter, activation of nuclear receptors, or histone H3 hyperacetylation. Indirectly, telomerase can also be modulated via activation of antioxidant defense pathways. Understanding telomerase reactivation and its modulation by BFCs is key to establishing effective HCC chemoprevention strategies targeting telomerase.