ArticleCell death & disease2017
Oroxylin A activates PKM1/HNF4 alpha to induce hepatoma differentiation and block cancer progression.
Article in Cell death & disease, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It has been retracted, and should not be counted. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 70 citations in OpenAlex.
- Oroxylin A may promote cell apoptosis and inhibit epithelial-mesenchymal transition in endometrial cancer, associated with the ERβ/PI3K/AKT pathway.Scientific reports · 2025Article
- Nerve Growth Factor Signaling Promotes Nuclear Translocation of TRAF4 to Enhance Tumor Stemness and Metastatic Dormancy Via C-Jun-mediated IL-8 Autocrine.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Clinical development and informatics analysis of natural and semi-synthetic flavonoid drugs: A critical review.Journal of advanced research · 2024Review
- Muscle-specific pyruvate kinase isoforms, PKM1 and PKM2, regulate mammalian SWI/SNF proteins and histone 3 phosphorylation during myoblast differentiation.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2024Article
- Muscle-Specific Pyruvate Kinase Isoforms, Pkm1 and Pkm2, Regulate Mammalian SWI/SNF Proteins and Histone 3 Phosphorylation During Myoblast Differentiation.bioRxiv : the preprint server for biology · 2024Article
- Review
- Anticancer potential of oroxylin A: from mechanistic insight to synergistic perspectives.Naunyn-Schmiedeberg's archives of pharmacology · 2023Review
- Targeting LRRC41 as a potential therapeutic approach for hepatocellular carcinoma.Frontiers in molecular biosciences · 2023Article
- Novel transketolase inhibitor oroxylin A suppresses the non-oxidative pentose phosphate pathway and hepatocellular carcinoma tumour growth in mice and patient-derived organoids.Clinical and translational medicine · 2022Article
- Caenorhabditis elegans NHR-14/HNF4α regulates DNA damage-induced apoptosis through cooperating with cep-1/p53.Cell communication and signaling : CCS · 2022Article
- Oroxylin A: A Promising Flavonoid for Prevention and Treatment of Chronic Diseases.Biomolecules · 2022Review
- Article
- Targeting cyclin-dependent kinase 9 in cancer therapy.Acta pharmacologica Sinica · 2022Review
- Novel CDK9 inhibitor oroxylin A promotes wild-type P53 stability and prevents hepatocellular carcinoma progression by disrupting both MDM2 and SIRT1 signaling.Acta pharmacologica Sinica · 2022Article
- Natural products targeting glycolytic signaling pathways-an updated review on anti-cancer therapy.Frontiers in pharmacology · 2022Review
- Conjugated Linoleic Acid Treatment Attenuates Cancerous features in Hepatocellular Carcinoma Cells.Stem cells international · 2022Article
- Review
- Discovery of Functional Alternatively SplicedCancers · 2021Article
- Review
- The Potential Application of Chinese Medicine in Liver Diseases: A New Opportunity.Frontiers in pharmacology · 2021Review
Corrections and comments
- Retracted
Authors and funding
8 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Liver cancer is the second cause of death from cancer worldwide, without effective treatment. Traditional chemotherapy for liver cancer has big side effects for patients, whereas targeted drugs, such as sorafenib, commonly have drug resistance. Oroxylin A (OA) is the main bioactive flavonoids of Scutellariae radix, which has strong anti-hepatoma effect but low toxicity to normal tissue. To date, no differentiation-inducing agents have been reported to exert a curative effect on solid tumors. Here our results demonstrated that OA restrained the proliferation and induced differentiation of hepatoma both in vitro and in vivo, via inducing a high PKM1 (pyruvate kinase M1)/PKM2 (pyruvate kinase M2) ratio. In addition, inhibited expression of polypyrimidine tract-binding protein by OA was in charge of the decrease of PKM2 and increase of PKM1. Further studies demonstrated that increased PKM1 translocated into the nucleus and bound with HNF-4α (hepatocyte nuclear factor 4 alpha) directly, promoting the transcription of HNF-4α-targeted genes. This work suggested that OA increased PKM1/PKM2 ratio, resulting in HNF-4α activation and hepatoma differentiation. Especially, OA showed reliable anticancer effect on both human primary hepatocellular carcinoma cells and patient-derived tumor xenograft model for hepatoma, and slowed down the development of primary hepatoma, suggesting that OA could be developed into a novel differentiation inducer agent for hepatoma.
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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.