ArticleJournal of experimental & clinical cancer research : CR2015
Activation of SAPK/JNK mediated the inhibition and reciprocal interaction of DNA methyltransferase 1 and EZH2 by ursolic acid in human lung cancer cells.
Article in Journal of experimental & clinical cancer research : CR, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 37 citations in OpenAlex.
- Targeting the CTBP1-CETP axis overcomes ferroptosis resistance in non-small cell lung cancer by altering lipid accumulation.Clinical and translational medicine · 2026Article
- Natural modulators of enhancer of zeste homolog 2 (EZH2): potential epigenetic regulators of aging-associated pathways.Biogerontology · 2026Review
- Advances in the chemo‑preventive effects and mechanisms of ursolic acid against lung cancer (Review).Oncology reports · 2025Review
- Cucurbitacin B Inhibits the Proliferation of WPMY-1 Cells and HPRF Cells via the p53/MDM2 Axis.International journal of molecular sciences · 2024Article
- The roles of EZH2 in cancer and its inhibitors.Medical oncology (Northwood, London, England) · 2023Review
- Ursolic acid enhances autophagic clearance and ameliorates motor and non-motor symptoms in Parkinson's disease mice model.Acta pharmacologica Sinica · 2023Article
- Evidence of the Beneficial Effects of Ursolic Acid against Lung Cancer.Molecules (Basel, Switzerland) · 2022Review
- Natural Bioactive Compounds Targeting Epigenetic Pathways in Cancer: A Review on Alkaloids, Terpenoids, Quinones, and Isothiocyanates.Nutrients · 2021Review
- Causal roles of stress kinase JNK2 in DNA methylation and binge alcohol withdrawal-evoked behavioral deficits.Pharmacological research · 2021Article
- Nanoformulations of Ursolic Acid: A Modern Natural Anticancer Molecule.Frontiers in pharmacology · 2021Review
- Epigenetics/epigenomics of triterpenoids in cancer prevention and in health.Biochemical pharmacology · 2020Review
- Long noncoding RNA LINC01111 suppresses pancreatic cancer aggressiveness by regulating DUSP1 expression via microRNA-3924.Cell death & disease · 2019Article
- Caveolin-1 regulation of Sp1 controls production of the antifibrotic protein follistatin in kidney mesangial cells.Cell communication and signaling : CCS · 2019Article
- Ursolic Acid Exhibits Potent Anticancer Effects in Human Metastatic Melanoma Cancer Cells (SK-MEL-24) via Apoptosis Induction, Inhibition of Cell Migration and Invasion, Cell Cycle Arrest, and Inhibition of Mitogen-Activated Protein Kinase (MAPK)/ERK Signaling Pathway.Medical science monitor : international medical journal of experimental and clinical research · 2019Article
- Downregulated miR-144-3p contributes to progression of lung adenocarcinoma through elevating the expression of EZH2.Cancer medicine · 2018Article
- Correction to: In Vitro-In Vivo Dose Response of Ursolic Acid, Sulforaphane, PEITC, and Curcumin in Cancer Prevention.The AAPS journal · 2018Article
- The enhancement of combination of berberine and metformin in inhibition of DNMT1 gene expression through interplay of SP1 and PDPK1.Journal of cellular and molecular medicine · 2018Article
- In Vitro-In Vivo Dose Response of Ursolic Acid, Sulforaphane, PEITC, and Curcumin in Cancer Prevention.The AAPS journal · 2017Article
- A Case of Recurrent Hepatocellular Carcinoma Acquiring Complete Remission of Target Lesion With Treatment With Traditional Chinese Medicine.Integrative cancer therapies · 2017Article
- Long noncoding RNA XIST promotes malignancies of esophageal squamous cell carcinoma via regulation of miR-101/EZH2.Oncotarget · 2017Article
Corrections and comments
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundUrsolic acid (UA), a pentacyclic triterpenoid, is known to have anti-tumor activity in various cancers including human non small cell lung cancer (NSCLC). However, the molecular mechanisms underlying the action of UA remain largely unknown.
methodsCell viability was measured by MTT assays. Apoptosis was analyzed with Annexin V-FITC/PI Apoptosis Detection Kit by Flow cytometry. Western blot analysis was performed to measure the phosphorylation and protein expression of stress-activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK), DNMT1 [DNA (cytosine-5)-methyltransferase 1], enhancer of zeste 2 polycomb repressive complex 2 subunit (EZH2) and SP1. Exogenous expression of SP1 and DNMT1 was carried out by transient transfection assays.
resultsWe showed that UA inhibited the growth and induced apoptosis of NSCLC cells in the dose- and time-dependent fashion. Furthermore, we found that UA induced phosphorylation of SAPK/JNK and suppressed the protein expression of DNMT1 and EZH2. The inhibitor of SAPK/JNK (SP600125) blocked the UA-reduced expression of DNMT1 and EZH2. In addition, UA suppressed the expression of SP1 protein. Conversely, overexpression of SP1 reversed the effect of UA on DNMT1 and EZH2 expression, and feedback attenuated UA-induced phosphorylation of SAPK/JNK. Moreover, exogenous expression of DNMT1 antagonized the effect of UA on SAPK/JNK signaling, EZH2 protein expression, and NSCLC cell growth.
conclusionOur results show that UA inhibits growth of NSCLC cells through SAPK/JNK-mediated inhibition of SP1; this in turn results in inhibition the expression of DNMT1 and EZH2. Overexpression of DNMT1 diminishes UA-reduced EZH2 protein expression. The negative feedback regulation of SAPK/JNK signaling by SP1 and DNMT1, and the reciprocal interaction of EZH2 and DNMT1 contribute to the overall effects of UA. This study leads to important new insights into the mechanisms by which UA controls growth of NSCLC cells.
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