ArticleScientific reports2014
Synergism of ursolic acid derivative US597 with 2-deoxy-D-glucose to preferentially induce tumor cell death by dual-targeting of apoptosis and glycolysis.
Article in Scientific reports, 2014. 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, 72 citations in OpenAlex.
- Ursolic acid in cancer therapy: a review of signaling pathways and apoptotic mechanisms.Molecular biology reports · 2026Review
- Radiotherapy resistance in glioblastoma: Mechanistic insights and novel therapeutic approaches (Review).International journal of oncology · 2026Review
- Investigating the In Vitro Mitochondria-Mediated Anticancer Activity of the Plant Metabolite Ursolic Acid.International journal of molecular sciences · 2026Article
- Cytotoxicity ofInternational journal of molecular sciences · 2025Article
- Ursolic Acid's Alluring Journey: One Triterpenoid vs. Cancer Hallmarks.Molecules (Basel, Switzerland) · 2023Review
- Progress in Antimelanoma Research of Natural Triterpenoids and Their Derivatives: Mechanisms of Action, Bioavailability Enhancement and Structure Modifications.Molecules (Basel, Switzerland) · 2023Review
- How Should the Worldwide Knowledge of Traditional Cancer Healing Be Integrated with Herbs and Mushrooms into Modern Molecular Pharmacology?Pharmaceuticals (Basel, Switzerland) · 2022Review
- A network-biology led computational drug repurposing strategy to prioritize therapeutic options for COVID-19.Heliyon · 2022Article
- The Presence of a Cyclohexyldiamine Moiety Confers Cytotoxicity to Pentacyclic Triterpenoids.Molecules (Basel, Switzerland) · 2021Article
- Screening of metabolic modulators identifies new strategies to target metabolic reprogramming in melanoma.Scientific reports · 2021Article
- All-in-one mitochondria-targeted NIR-II fluorophores for cancer therapy and imaging.Chemical science · 2020Article
- Evolution from small molecule to nano-drug delivery systems: An emerging approach for cancer therapy of ursolic acid.Asian journal of pharmaceutical sciences · 2020Review
- Triple Negative Breast Cancer and Breast Epithelial Cells Differentially Reprogram Glucose and Lipid Metabolism upon Treatment with Triterpenic Acids.Biomolecules · 2020Article
- Mitochondria-targeting fluorescent molecules for high efficiency cancer growth inhibition and imaging.Chemical science · 2019Article
- Anticancer effect of ursolic acid via mitochondria-dependent pathways.Oncology letters · 2019Review
- Isolation of 4,4'-bond secalonic acid D from the marine-derived fungus Penicillium oxalicum with inhibitory property against hepatocellular carcinoma.The Journal of antibiotics · 2019Article
- Iso-pencillixanthone A from a marine-derived fungus reverses multidrug resistance in cervical cancer cells through down-regulating P-gp and re-activating apoptosis.RSC advances · 2018Article
- Synthesis and Evaluation of Anticancer Activities of Novel C-28 Guanidine-Functionalized Triterpene Acid Derivatives.Molecules (Basel, Switzerland) · 2018Article
- Ursolic acid-mediated changes in glycolytic pathway promote cytotoxic autophagy and apoptosis in phenotypically different breast cancer cells.Apoptosis : an international journal on programmed cell death · 2017Article
- Review
Corrections and comments
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Authors and funding
12 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Ursolic acid (UA) is a naturally bioactive product that exhibits potential anticancer effects. The relatively safe and effective molecule intrigued us to explore a way to further improve its anti-cancer activity and tumor-targeting specificity. In the present study, a series of structural modifications of UA was achieved, which resulted in significant increase in growth inhibition on various cancer cell lines with minimal effects on normal cells. The leading molecule US597 (UA-4) caused depolarization of mitochondrial membrane potential, cell arrest in G0/G1 phase and apoptosis/necrosis in a dose-dependent manner. Structural docking suggested that the carbon chains of the modified UA derivatives compete strongly with glucose for binding to glucokinase, the key glycolysis enzyme presumably active in cancer cells. The combination of 2-deoxy-D-glucose (2-DG) and UA-4 induced cell cycle arrest in G2/M phase, promoted caspase-dependent cell death, reduced hexokinase activity, aggravated depletion of intracellular ATP, decreased lactate production and synergistically inhibited cancer cell growth in vitro (HepG2) and in vivo (H22). Collectively, our findings suggest that the structural modification enhances efficacy and selectivity of UA, and the combination of UA-4 with 2-DG produces synergistic inhibition on hepatoma cell proliferation by dual targeting of apoptosis and glycolysis.
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