Food Compounds That Target Telomerase May Help Prevent Liver Cancer
A systematic review reveals how bioactive food compounds modulate telomerase activity to potentially prevent hepatocellular carcinoma.
Summary
Researchers from the University of São Paulo conducted a systematic review examining how bioactive food compounds (BFCs) — including fatty acids, isoprenoids, isothiocyanates, and phenolic compounds — influence telomerase activity during hepatocarcinogenesis. Telomere shortening is a known driver of liver cirrhosis and eventual hepatocellular carcinoma (HCC), while telomerase reactivation at later cancer stages accelerates tumor progression. The review found that despite their structural diversity, these food-derived compounds share common molecular mechanisms: inhibiting activating proteins at the TERT promoter, activating nuclear receptors, and promoting histone H3 hyperacetylation. Antioxidant pathway activation also indirectly modulates telomerase. These findings suggest dietary compounds may serve as viable chemopreventive tools against one of the world's deadliest cancers.
Detailed Summary
Hepatocellular carcinoma (HCC) is among the most lethal and prevalent cancers globally, and its development is deeply intertwined with telomere biology. Telomere shortening accelerates chromosomal instability, promoting preneoplastic liver conditions like cirrhosis, while subsequent telomerase reactivation enables malignant cells to achieve replicative immortality. Mutations in the TERT promoter — encoding a key telomerase subunit — are among the most common genetic alterations in human cancers, making this pathway a compelling chemopreventive target.
This systematic review, conducted by researchers at the University of São Paulo and Federal University of Goiás, investigated whether bioactive food compounds (BFCs) can modulate telomerase activity across stages of hepatocarcinogenesis. BFCs were categorized into four structural classes: fatty acids, isoprenoids, isothiocyanates, and phenolic compounds — all naturally occurring in fruits, vegetables, seeds, and oils.
Despite their chemical diversity, the reviewed BFCs converged on shared molecular mechanisms. These include inhibition of transcription factors that activate the TERT promoter, activation of nuclear receptors that suppress telomerase expression, and histone H3 hyperacetylation that alters chromatin accessibility at telomerase-related gene loci. Indirectly, BFCs may also modulate telomerase through upregulation of antioxidant defense pathways, reducing oxidative stress that can drive telomere attrition.
The findings carry meaningful implications for cancer prevention strategies. Rather than waiting for HCC to develop, targeting telomerase during cirrhosis or early dysplastic nodule formation — stages where BFCs may suppress aberrant telomerase activation — could interrupt hepatocarcinogenesis before it becomes irreversible.
Key caveats include reliance on preclinical and in vitro evidence for most BFCs reviewed, limited human clinical trial data, and the challenge of achieving relevant tissue concentrations through diet alone. Nonetheless, this work lays important groundwork for future nutritional chemoprevention trials targeting telomerase in high-risk HCC populations.
Key Findings
- Telomere shortening drives cirrhosis; telomerase reactivation later enables HCC tumor immortality.
- Bioactive food compounds from four structural classes all modulate telomerase via shared mechanisms.
- Key mechanisms include TERT promoter inhibition, nuclear receptor activation, and histone H3 hyperacetylation.
- Antioxidant pathway activation by BFCs indirectly reduces telomere attrition and telomerase dysregulation.
- Dietary compounds may be most effective as chemopreventives during early preneoplastic liver disease stages.
Methodology
This was a systematic review of published literature on bioactive food compounds and their effects on telomerase activity during hepatocarcinogenesis. BFCs were categorized into fatty acids, isoprenoids, isothiocyanates, and phenolic compounds. The review synthesized findings from preclinical, in vitro, and available human studies.
Study Limitations
The review is largely based on preclinical and in vitro data, limiting direct clinical applicability. Bioavailability and effective tissue concentrations of BFCs through normal dietary intake remain uncertain. Human clinical trials specifically targeting telomerase modulation via BFCs in HCC-risk populations are sparse.
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