ArticleRedox biology2020
Polyphenolic Proanthocyanidin-B2 suppresses proliferation of liver cancer cells and hepatocellular carcinogenesis through directly binding and inhibiting AKT activity.
Article in Redox biology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
36 citing papers in PubMed, 1 synthesis or guideline pooled it, 70 citations in OpenAlex.
- Therapeutic Effects of Natural Products on Liver Cancer and Their Potential Mechanisms.Nutrients · 2024Pooled it
- Fractionation-Based Modeling of Hawthorn (Molecules (Basel, Switzerland) · 2026Article
- Integrating Network Pharmacology and Experimental Validation to Elucidate the Role of Huaier in Attenuating Liver Fibrosis via the AKT Signalling Pathway.Clinical and experimental medicine · 2026Article
- STOML2 promotes hepatocellular carcinoma cell proliferation, invasion and migration by activating the PI3K/AKT signaling pathway (Review).Oncology letters · 2026Review
- UHPLC-QTOF-MS/MS-based metabolomic discovery of anticancer compounds in ethanolic extracts of Ficus hispida L. f.PloS one · 2026Article
- Two WD40 proteins, AhWD40-170 and AhWD40-171, referred to regulation of anthocyanin accumulation in peanut (Arachis hypogaea L.).BMC plant biology · 2025Article
- Oligomeric Proanthocyanidins Reverse Lenvatinib Resistance in Hepatocellular Carcinoma Through ITGA3-Mediated Pathway.Pharmaceuticals (Basel, Switzerland) · 2025Article
- Immune Escape-Related Gene NXT1 as a Potential Prognostic and Therapeutic Target in Hepatocellular Carcinoma.The Turkish journal of gastroenterology : the official journal of Turkish Society of Gastroenterology · 2025Article
- Nanoengineered hydrogels disrupt tumor antioxidant defense via photothermal-chemodynamic synergy and oxidative stress boosts.Journal of nanobiotechnology · 2025Article
- Article
- Peanut skin polyphenols inhibit proliferation of leukemia cells in vitro, and its A-type procyanidins selectively pass through a Caco-2 intestinal barrier.Journal of food science · 2025Article
- Dietary polyphenols and human health: sources, biological activities, nutritional and immunological aspects, and bioavailability- a comprehensive review.Frontiers in immunology · 2025Review
- Unlocking the mechanistic potential ofJournal of traditional and complementary medicine · 2024Review
- Polyphenols: Secondary Metabolites with a Biological Impression.Nutrients · 2024Review
- Phylogenomic Analysis ofGenes · 2023Article
- The combined anticancer of peanut skin procyanidins and resveratrol to CACO-2 colorectal cancer cells.Food science & nutrition · 2023Article
- Protein and Peptide-Based Nanotechnology for Enhancing Stability, Bioactivity, and Delivery of Anthocyanins.Advanced healthcare materials · 2023Review
- [Dealcoholized red wine inhibits occurrence and progression of hepatocellular carcinoma possibly by inducing cell cycle arrest and apoptosis].Nan fang yi ke da xue xue bao = Journal of Southern Medical University · 2023Article
- Oligomeric Proanthocyanidins: An Updated Review of Their Natural Sources, Synthesis, and Potentials.Antioxidants (Basel, Switzerland) · 2023Review
- Possible Side Effects of Polyphenols and Their Interactions with Medicines.Molecules (Basel, Switzerland) · 2023Review
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The well-documented anticarcinogenic properties of natural polyphenolic proanthocyanidins (OPC) have been primarily attributed to their antioxidant and anti-inflammatory potency. Emerging evidence suggests that OPC may target canonical oncogenic pathways, including PI3K/AKT; however, the underlying mechanism and therapeutic potential remain elusive. Here we identify that proanthocyanidin B2 (OPC-B2) directly binds and inhibits AKT activity and downstream signalling, thereby suppressing tumour cell proliferation and metabolism in vitro and in a xenograft and diethyl-nitrosamine (DEN)-induced hepatocellular carcinoma (HCC) mouse models. We further find that OPC-B2 binds to the catalytic and regulatory PH domains to lock the protein in a closed conformation, similar to the well-studied AKT allosteric inhibitor MK-2206. Molecular docking and dynamic simulation suggest that Lys297 and Arg86 are critical sites of OPC-B2 binding; mutation of Lys297 or Arg86 to alanine completely abolishes the antitumor effects of OPC-B2 but not MK-2206. Together, our study reveals that OPC-B2 is a novel allosteric AKT inhibitor with potent anti-tumour efficacy beyond its antioxidant and anti-inflammatory properties.
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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.