ArticleMolecular carcinogenesis2015
Grape seed extract and resveratrol prevent 4-nitroquinoline 1-oxide induced oral tumorigenesis in mice by modulating AMPK activation and associated biological responses.
Article in Molecular carcinogenesis, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers, 1 of them a synthesis that pooled it.
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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.
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.
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Who cites it
18 citing papers in PubMed, 1 synthesis or guideline pooled it, 44 citations in OpenAlex.
- A systematic review and meta-analysis of the impact of resveratrol on oral cancer: potential therapeutic implications.BMC oral health · 2024Pooled it
- Article
- An Updated Narrative Review on the Therapeutic Potential of Resveratrol in the Treatment of Cancer.Health science reports · 2026Article
- Stilbenes from Vine Extracts: Therapeutic Potential and Mechanisms.International journal of molecular sciences · 2025Review
- Beyond Conventional Treatments: The Role of Complementary Therapies in Head and Neck Cancer.Cancers · 2025Review
- Anticancer Activity and Molecular Targets ofBiomedicines · 2023Article
- The role of AMPK in cancer metabolism and its impact on the immunomodulation of the tumor microenvironment.Frontiers in immunology · 2023Review
- Resveratrol effects in oral cancer cells: a comprehensive review.Medical oncology (Northwood, London, England) · 2021Review
- Resveratrol: Twenty Years of Growth, Development and Controversy.Biomolecules & therapeutics · 2019Review
- Mouse Models for Studying Oral Cancer: Impact in the Era of Cancer Immunotherapy.Journal of dental research · 2018Review
- Grape seed proanthocyanidins inhibit the proliferation, migration and invasion of tongue squamous cell carcinoma cells through suppressing the protein kinase B/nuclear factor-κB signaling pathway.International journal of molecular medicine · 2017Article
- Bioactivity-based antioxidative components screening and evaluation in grape seed proanthocyanidin extract.Journal of food science and technology · 2017Article
- Inhibitory Growth of Oral Squamous Cell Carcinoma Cancer via Bacterial Prodigiosin.Marine drugs · 2017Article
- Trans-scirpusin A showed antitumor effects via autophagy activation and apoptosis induction of colorectal cancer cells.Oncotarget · 2017Article
- GSPE Inhibits HMGB1 Release, Attenuating Renal IR-Induced Acute Renal Injury and Chronic Renal Fibrosis.International journal of molecular sciences · 2016Article
- Role of Natural Stilbenes in the Prevention of Cancer.Oxidative medicine and cellular longevity · 2016Review
- Regulation of AMP-activated protein kinase by natural and synthetic activators.Acta pharmaceutica Sinica. B · 2016Review
- Esophageal Cancer: Insights From Mouse Models.Cancer growth and metastasis · 2015Review
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
Preventive measures against oral carcinogenesis are urgently warranted to lower the high morbidity and mortality associated with this malignancy worldwide. Here, we investigated the chemopreventive efficacy of grape seed extract (GSE) and resveratrol (Res) in 4-nitroquinoline-1-oxide (4NQO)-induced tongue tumorigenesis in C57BL/6 mice. Following 8 weeks of 4NQO exposure (100 µg/ml in drinking water), mice were fed with either control AIN-76A diet or diet containing 0.2% GSE (w/w) or 0.25% Res (w/w) for 8 subsequent weeks, while continued on 4NQO. Upon termination of the study at 16 weeks, tongue tissues were histologically evaluated for hyperplasia, dysplasia, and papillary lesions, and then analyzed for molecular targets by immunohistochemistry. GSE and Res feeding for 8 weeks, moderately decreased the incidence, but significantly prevented the multiplicity and severity of 4NQO-induced preneoplastic and neoplastic lesions, without any apparent toxicity. In tongue tissues, both 4NQO + GSE and 4NQO + Res treatment correlated with a decreased proliferation (BrdU labeling index) but increased apoptotic death (TUNEL-positive cells) as compared to the 4NQO group. Furthermore, tongue tissues from both the 4NQO + GSE and 4NQO + Res groups showed an increase in activated metabolic regulator phospho-AMPK (Thr172) and decreased autophagy flux marker p62. Together, these findings suggest that GSE and Res could effectively prevent 4NQO-induced oral tumorigenesis through modulating AMPK activation, and thereby, inhibiting proliferation and inducing apoptosis and autophagy, as mechanisms of their efficacy.
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Registered trials
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.