ArticleScientific reports2020
Hemistepsin A suppresses colorectal cancer growth through inhibiting pyruvate dehydrogenase kinase activity.
Article in Scientific reports, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 32 citations in OpenAlex.
- Mechanistic insights into polyphenolic constituents from traditional Chinese medicines in inhibiting colorectal cancer metastasis.Natural products and bioprospecting · 2026Review
- Isoimperatorin suppresses triple-negative breast cancer by modulating miR-874-3p/POU2F1 axis: a new avenue for metabolic and redox intervention.Biological research · 2026Article
- Lactate metabolism and protein lactylation in colorectal cancer: from metabolic reprogramming to epigenetic regulation.Frontiers in oncology · 2026Review
- Hemistepsin A induces apoptosis by modulating the reactive oxygen species-dependent PI3K/Akt signaling pathway in human lung carcinoma A549 cells.The Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology · 2025Article
- Energy metabolism in health and diseases.Signal transduction and targeted therapy · 2025Review
- Natural Products and Derivatives Targeting Metabolic Reprogramming in Colorectal Cancer: A Comprehensive Review.Metabolites · 2024Review
- p53 Orchestrates Cancer Metabolism: Unveiling Strategies to Reverse the Warburg Effect.Bulletin of mathematical biology · 2024Article
- Adverse maternal and neonatal outcomes of preimplantation genetic testing with trophectoderm biopsy: a retrospective cohort study of 3373 intracytoplasmic sperm injection single frozen-thawed blastocyst transfer cycles.Archives of gynecology and obstetrics · 2024Article
- Targeting pyruvate dehydrogenase kinase 1 overcomes EGFR C797S mutation-driven osimertinib resistance in non-small cell lung cancer.Experimental & molecular medicine · 2024Article
- Natural Product-Based Glycolysis Inhibitors as a Therapeutic Strategy for Epidermal Growth Factor Receptor-Tyrosine Kinase Inhibitor-Resistant Non-Small Cell Lung Cancer.International journal of molecular sciences · 2024Review
- Targeting the mTOR Pathway in Hepatocellular Carcinoma: The Therapeutic Potential of Natural Products.Journal of inflammation research · 2024Review
- A novel organic arsenic derivative MZ2 remodels metabolism and triggers mtROS-mediated apoptosis in acute myeloid leukemia.Journal of cancer research and clinical oncology · 2023Article
- Andrographolide suppresses aerobic glycolysis and induces apoptotic cell death by inhibiting pyruvate dehydrogenase kinase 1 expression.Oncology reports · 2023Article
- AAZ2 induces mitochondrial-dependent apoptosis by targeting PDK1 in gastric cancer.Journal of Zhejiang University. Science. B · 2023Article
- Phytochemicals targeting glycolysis in colorectal cancer therapy: effects and mechanisms of action.Frontiers in pharmacology · 2023Review
- Targeting Energy Metabolism in Cancer Treatment.International journal of molecular sciences · 2022Review
- A comprehensive analysis of the prognostic value and immune infiltration of low expression DBT in clear cell renal cell carcinoma.Frontiers in pharmacology · 2022Article
- Inhibition of Autophagy Promotes Hemistepsin A-Induced Apoptosis via Reactive Oxygen Species-Mediated AMPK-Dependent Signaling in Human Prostate Cancer Cells.Biomolecules · 2021Article
- Drug evaluation based on phosphomimetic PDHA1 reveals the complexity of activity-related cell death in A549 non-small cell lung cancer cells.BMB reports · 2021Article
- Pyruvate dehydrogenase E1α represents a reliable prognostic predictor for patients with non-small cell lung cancer resected via curative operation.Journal of thoracic disease · 2021Article
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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
Most cancer cells primarily produce their energy through a high rate of glycolysis followed by lactic acid fermentation even in the presence of abundant oxygen. Pyruvate dehydrogenase kinase (PDK) 1, an enzyme responsible for aerobic glycolysis via phosphorylating and inactivating pyruvate dehydrogenase (PDH) complex, is commonly overexpressed in tumors and recognized as a therapeutic target in colorectal cancer. Hemistepsin A (HsA) is a sesquiterpene lactone isolated from Hemistepta lyrata Bunge (Compositae). Here, we report that HsA is a PDK1 inhibitor can reduce the growth of colorectal cancer and consequent activation of mitochondrial ROS-dependent apoptotic pathway both in vivo and in vitro. Computational simulation and biochemical assays showed that HsA directly binds to the lipoamide-binding site of PDK1, and subsequently inhibits the interaction of PDK1 with the E2 subunit of PDH complex. As a result of PDK1 inhibition, lactate production was decreased, but oxygen consumption was increased. Mitochondrial ROS levels and mitochondrial damage were also increased. Consistent with these observations, the apoptosis of colorectal cancer cells was promoted by HsA with enhanced activation of caspase-3 and -9. These results suggested that HsA might be a potential candidate for developing a novel anti-cancer drug through suppressing cancer metabolism.
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