ArticleJournal of experimental & clinical cancer research : CR2019
PKM2 is the target of proanthocyanidin B2 during the inhibition of hepatocellular carcinoma.
Article in Journal of experimental & clinical cancer research : CR, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 papers, 1 of them a synthesis that pooled it.
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Who cites it
60 citing papers in PubMed, 1 synthesis or guideline pooled it, 106 citations in OpenAlex.
- Natural products targeting glycolysis in cancer.Frontiers in pharmacology · 2022Pooled it
- Targeting Pyruvate Kinase M2: Signal Transduction Pathways and Exploration of Cancer Therapeutic Strategies.The AAPS journal · 2026Review
- Metabolic-photoimmunotherapy: A Shikonin-NIR-I photosensitizer nanoplatform reprograms glycolysis to potentiate phototherapy-induced antitumor immunity in hepatocellular carcinoma.Materials today. Bio · 2026Article
- The moonlighting functions of glycolytic enzymes in tumorigenesis.Cellular oncology (Dordrecht, Netherlands) · 2026Review
- Targeting aerobic glycolysis combats tyrosine kinase inhibitor resistance of hepatocellular carcinoma.International journal of cancer · 2026Review
- Metabolic reprogramming-driven resistance to multi-kinase inhibitors in hepatocellular carcinoma: molecular mechanisms and therapeutic opportunities.Molecular cancer · 2026Review
- Exosome-Mediated Regulation of Aerobic Glycolysis in Hepatocellular Carcinoma: Mechanisms and Therapeutic Implications.Journal of hepatocellular carcinoma · 2026Review
- The proteostasis paradox: from systemic collapse in aging to pathway-specific addiction in prostate cancer.Frontiers in cell and developmental biology · 2026Review
- Procyanidin Suppresses Tumor Growth by Activating the B-Cell MAPK Pathway through Remodulation of the Gut Microbiota and Metabolites in Hepatocellular Carcinoma.International journal of biological sciences · 2026Article
- Electroacupuncture and Moxibustion Regulate Aerobic Glycolysis and Alleviate Tumor Progression in Mice with Hepatocellular Carcinoma.Journal of hepatocellular carcinoma · 2026Article
- Nuclear translocation of pyruvate kinase M2 drives high glucose-induced angiogenesis in retinal endothelial cellsInternational journal of ophthalmology · 2026Article
- Flavonoid Composition and Bioactivities ofLife (Basel, Switzerland) · 2025Article
- The effect of glycolytic enzyme expression and thyroiditis on the aggressiveness of papillary thyroid carcinoma: a retrospective cohort study.Annals of surgical treatment and research · 2025Article
- Long non-coding RNAJournal of biomedical research · 2025Article
- Proanthocyanidin B2 alleviatesCytotechnology · 2025Article
- Metabolic reprogramming and immunological changes in the microenvironment of esophageal cancer: future directions and prospects.Frontiers in immunology · 2025Review
- PFKL Inhibition by DT-13: A Novel Approach to Combat Hepatocellular Carcinoma.International journal of hepatology · 2025Article
- Metabolic reprogramming of glucose: the metabolic basis for the occurrence and development of hepatocellular carcinoma.Frontiers in oncology · 2025Review
- Flavonoids as modulators of metabolic reprogramming in renal cell carcinoma (Review).Oncology reports · 2024Review
- The regulatory roles and clinical significance of glycolysis in tumor.Cancer communications (London, England) · 2024Review
Corrections and comments
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Authors and funding
13 authors at 4 institutions in 1 country.
Funding
Abstract
backgroundThe treatment for advanced primary hepatocellular carcinoma (HCC) is sorafenib (SORA), while HCC has become increasingly drug resistant with enhanced aerobic glycolysis. The present study aimed to examine the chemotherapeutic effects of a flavonoid proanthocyanidin B2 (PB2) on HCC.
methodsFive kinds of HCC cell lines and LO2 were used to test the effect of PB2 on aerobic glycolysis. The proliferation, cell cycle, apoptosis and a xenograft mouse model were analyzed. Lentivirus overexpressed pyruvate kinase M2 (PKM2) or sh-PKM2 was used to verify the target of PB2. The detailed mechanism was investigated by immunofluorescence, co-immunoprecipitation, and western blotting.
resultsPB2 inhibited the proliferation, induced cell cycle arrest, and triggered apoptosis of HCC cells in vivo and in vitro. PB2 also suppressed glucose uptake and lactate levels via the direct inhibition of the key glycolytic enzyme, PKM2. In addition, PKM2 inhibited the nuclear translocation of PKM2 and co-localization of PKM2/HIF-1α in the nucleus, leading to the inhibition of aerobic glycolysis. Co-treatment with PB2 was also effective in enhancing the chemosensitivity of SORA.
conclusionsPB2 inhibited the expression and nuclear translocation of PKM2, therefore disrupting the interaction between PKM2/HSP90/HIF-1α, to suppress aerobic glycolysis and proliferation, and trigger apoptosis in HCC via HIF-1α-mediated transcription suppression.
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