Evidence map›Paper›PMID 40888265›Full record

ArticleMolecular nutrition & food research2025

AMPK-Dependent Epigenetic Regulation of Metabolism Mediates the Anti-Cancer Action of Pterostilbene in Hepatocellular Carcinoma.

Cayla Boycott, Megan Beetch, Katarzyna Lubecka-Gajewska, Benjamin S Ramsey, Sandra Torregrosa-Allen, Bennett D Elzey, Abigail Cox, Nadia Atallah Lanman, Aline de Conti, Min Li and 3 more

Abstract read
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In one paragraph

Article in Molecular nutrition & food research, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

7 citing papers in PubMed.

  1. Article
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

13 authors.

Cayla BoycottFood, Nutrition and Health Program, Faculty of Land and Food Systems, The University of British Columbia, Vancouver, British Columbia, Canada.
Megan BeetchFood, Nutrition and Health Program, Faculty of Land and Food Systems, The University of British Columbia, Vancouver, British Columbia, Canada.
Katarzyna Lubecka-GajewskaDepartment of Biomedical Chemistry, Faculty of Health Sciences, Medical University of Lodz, Lodz, Poland.
Benjamin S RamseyPurdue University Institute For Cancer Research, Purdue University, West Lafayette, Indiana, USA.
Sandra Torregrosa-AllenPurdue University Institute For Cancer Research, Purdue University, West Lafayette, Indiana, USA.
Bennett D ElzeyPurdue University Institute For Cancer Research, Purdue University, West Lafayette, Indiana, USA.
Abigail CoxDepartment of Comparative Pathobiology, College of Veterinary Medicine, Purdue University, West Lafayette, Indiana, USA.
Nadia Atallah LanmanPurdue University Institute For Cancer Research, Purdue University, West Lafayette, Indiana, USA.
Aline de ContiInternational Agency for Research on Cancer, IARC, Lyon, France.
Min LiDepartment of Food Science, Purdue University, West Lafayette, Indiana, USA.
Mario FerruzziCollege of Agriculture and Life Sciences, Virginia Tech, Blacksburg, Virginia, USA.
Igor PogribnyDivision of Biochemical Toxicology, FDA-National Center for Toxicological Research, Jefferson, Arkansas, USA.
Barbara StefanskaFood, Nutrition and Health Program, Faculty of Land and Food Systems, The University of British Columbia, Vancouver, British Columbia, Canada.ORCID 0000-0002-1186-3210

Funding

Alliance International Collaboration ALLRP 5971BC Knowledge Development Fund #37105Biological Evaluation Shared ResourceCanada Foundation for Innovation John R. Evans Leadership Fund #37105Collaborative Core for Cancer BioinformaticsComputational Genomics Shared ResourceDiscovery Launch Supplement DGECR-2021-00286IU Simon Comprehensive Cancer CenterMedical University of Lodz 503/6-099-01/503-61-01Natural Sciences and Engineering Research Council (NSERC) Discovery RGPIN-2021-02969USDA National Institute of Food and Agriculture Hatch project 1005656Walther Cancer FoundationWorld Health Organization 001
6 · The paper itself

Abstract

Disrupted metabolism, often implicated in hepatocellular carcinoma (HCC), is linked to aberrant epigenetic patterns. Dietary polyphenols, including pterostilbene (PTS), have been demonstrated to remodel epigenetic landscapes and restore metabolic homeostasis by regulating the activity of AMP-activated protein kinase (AMPK), a protein recently shown to orchestrate a diverse set of networks to epigenetically mediate transcription. We therefore explored the mechanistic involvement of AMPK in the epigenetic effects of PTS in HCC. We incorporated PTS into a choline-deficient amino acid defined HCC-inducing diet (CDAA) in male Fisher-344 rats and found significant attenuation in HCC development compared to CDAA alone. Transcriptomics by RNA-sequencing revealed PTS-upregulated targets, that were enriched in key metabolic processes, including the folate (Aldh1l1), methionine (Bhmt), and sarcosine (Dmdgh) cycles. PTS-mediated gene upregulation was linked to lower levels of histone H3-methylation at lysine 27 (H3K27me3) at gene promoters. Mechanistic studies in HCC HepG2 cells revealed that AMPK inhibition abolished epigenetic gene activation in response to PTS, which was accompanied by diminished binding of H3K27me3-demethylase KDM6A at promoters of PTS-target genes. Our findings provide evidence for new disease vulnerabilities that arise from epigenetic/metabolic changes and constitute novel opportunities for preventative and therapeutic success in HCC.

Indexed as

AMP-Activated Protein KinasesCarcinoma, HepatocellularEpigenesis, GeneticLiver NeoplasmsStilbenesAnimalsHep G2 CellsHistonesHumansMaleRatsRats, Inbred F344AMP-Activated Protein KinasesHistonespterostilbeneStilbenesAMPKepigeneticshistone demethylase KDM6Aliver cancerpterostilbenetranscriptomics

Identifiers

PMID40888265
PMCPMC12666732

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.