ArticleClinical and translational medicine2022
Novel transketolase inhibitor oroxylin A suppresses the non-oxidative pentose phosphate pathway and hepatocellular carcinoma tumour growth in mice and patient-derived organoids.
Article in Clinical and translational medicine, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 36 citations in OpenAlex.
- Safety and pharmacokinetics evaluation of oroxylin A in Chinese healthy volunteers: a phase I, double-blind, placebo-controlled, single ascending dose, multiple dose, and food effect study.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026Trial
- Article
- Cuproptosis-Related Genes in Immune Infiltration and Diagnosis in Hepatitis B Virus-Related Acute Liver Failure.Exploration (Beijing, China) · 2026Article
- Reassessing Transketolase Assays: Methodological Considerations for Detecting Functional Thiamine Deficiency.Annals of the New York Academy of Sciences · 2026Review
- Investigating Coenzyme Function of Thiamine Triphosphate Using Its Novel Hydrolysis-Resistant Analog and Transketolase.Biomolecules · 2026Article
- Metabolic reprogramming in cancer: signaling pathways and therapeutic targets.Molecular cancer · 2026Review
- Natural Products in Cancer Prevention and Therapy: Current Challenges and Future Directions.MedComm · 2026Review
- SIRT3 activation by oroxylin A phosphate diethyl ester triggers mitochondrial dysfunction and apoptosis in non-small cell lung cancer.International journal of biological sciences · 2026Article
- Article
- IL21-STAT3 controls the pentose phosphate pathway to support metabolic reprogramming and tumor progression in chronic lymphocytic leukemia.HemaSphere · 2026Article
- Structural and Computational Insights into Transketolase-like 1 (TKTL-1): Distinction from TKT and Implications for Cancer Metabolism and Therapeutic Targeting.Molecules (Basel, Switzerland) · 2025Article
- A novel effect of sulforaphane on promoting mouse granulosa cells proliferation via the NRF2-TKT pathway.Journal of advanced research · 2025Article
- Chaetocin, a Natural Inhibitor of Transketolase, Suppresses the Non-Oxidative Pentose Phosphate Pathway and Inhibits the Growth of Drug-Resistant Non-Small Cell Lung Cancer.Antioxidants (Basel, Switzerland) · 2025Article
- HOXB4/METTL7B cascade mediates malignant phenotypes of hepatocellular carcinoma through TKT m6A modification.Biology direct · 2025Article
- Organoid, organ-on-a-chip and traditional Chinese medicine.Chinese medicine · 2025Review
- The Pentose Phosphate Pathway: From Mechanisms to Implications for Gastrointestinal Cancers.International journal of molecular sciences · 2025Review
- The role of transketolase in the immunotherapy and prognosis of hepatocellular carcinoma: a multi-omics approach.Frontiers in immunology · 2025Article
- Metabolic reprogramming of glucose: the metabolic basis for the occurrence and development of hepatocellular carcinoma.Frontiers in oncology · 2025Review
- Corynoline protects chronic pancreatitis via binding to PSMA2 and alleviating pancreatic fibrosis.Journal of gastroenterology · 2024Article
- Traditional Chinese medicine for the treatment of cancers of hepatobiliary system: from clinical evidence to drug discovery.Molecular cancer · 2024Review
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Authors and funding
16 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundTransketolase (TKT), a key rate-limiting enzyme in the non-oxidative branch of the pentose phosphate pathway (PPP), provides more than 85% of the ribose required for de novo nucleotide biosynthesis and promotes the development of hepatocellular carcinoma (HCC). Pharmacologic inhibition of TKT could impede HCC development and enhance treatment efficacy. However, no safe and effective TKT inhibitor has been approved.
methodsAn online two-dimensional TKT protein immobilised biochromatographic system was established for high-throughput screening of TKT ligands. Oroxylin A was found to specifically bind TKT. Drug affinity responsive target stability, cellular thermal shift assay, surface plasmon resonance, molecular docking, competitive displacement assay, and site mutation were performed to identify the binding of oroxylin A with TKT. Antitumour effects of oroxylin A were evaluated in vitro, in human xenograft mice, diethylnitrosamine (DEN)-induced HCC mice, and patient-derived organoids (PDOs). Metabolomic analysis was applied to detect the enzyme activity. Transcriptome profiling was conducted to illustrate the anti-HCC mechanism of oroxylin A. TKT knocking-down HCC cell lines and PDOs were established to evaluate the role of TKT in oroxylin A-induced HCC suppression.
resultsBy targeting TKT, oroxylin A stabilised the protein to proteases and temperature extremes, decreased its activity and expression, resulted in accumulation of non-oxidative PPP substrates, and activated p53 signalling. In addition, oroxylin A suppressed cell proliferation, induced apoptosis and cell-cycle arrest, and inhibited the growth of human xenograft tumours and DEN-induced HCC in mice. Crucially, TKT depletion exerted identical effects to oroxylin A, and the promising inhibitor also exhibited excellent therapeutic efficacy against clinically relevant HCC PDOs.
conclusionsThese results uncover a unique role for oroxylin A in TKT inhibition, which directly targets TKT and suppresses the non-oxidative PPP. Our findings will facilitate the development of small-molecule inhibitors of TKT and novel therapeutics for HCC.
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