ArticlePloS one2011
Suppression of STAT3 and HIF-1 alpha mediates anti-angiogenic activity of betulinic acid in hypoxic PC-3 prostate cancer cells.
Article in PloS one, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 94 citations in OpenAlex.
- The Inclusion of Dietary and Medicinal Mushrooms into Translational Oncology: Pros and Cons at the Molecular Level.International journal of molecular sciences · 2026Review
- Betulinic Acid and Betulin Suppress Melanoma Growth by Modulating Apoptosis and Autophagy via PI3K/AKT/mTOR and MAPK Pathways.International journal of molecular sciences · 2026Article
- The role of lipid metabolic interactions in reshaping the tumor microenvironment.Acta biochimica et biophysica Sinica · 2025Article
- Betulinic acid and obesity-related disorders.Frontiers in pharmacology · 2025Review
- Terpenoid-Mediated Targeting of STAT3 Signaling in Cancer: An Overview of Preclinical Studies.Biomolecules · 2024Review
- Nature's Elixir for Cancer Treatment: Targeting Tumor-induced Neovascularization.Current medicinal chemistry · 2024Review
- Chaga mushroom triterpenoids as adjuncts to minimally invasive cancer therapies: A review.Current research in toxicology · 2023Article
- SESN2 Knockdown Increases Betulinic Acid-Induced Radiosensitivity of Hypoxic Breast Cancer Cells.Cells · 2022Article
- Multifunctional Roles of Betulinic Acid in Cancer Chemoprevention: Spotlight on JAK/STAT, VEGF, EGF/EGFR, TRAIL/TRAIL-R, AKT/mTOR and Non-Coding RNAs in the Inhibition of Carcinogenesis and Metastasis.Molecules (Basel, Switzerland) · 2022Review
- Betulinic Acid Affects the Energy-Related Proteomic Profiling in Pancreatic Ductal Adenocarcinoma Cells.Molecules (Basel, Switzerland) · 2021Article
- Betulinic Acid Suppresses Breast Cancer Metastasis by Targeting GRP78-Mediated Glycolysis and ER Stress Apoptotic Pathway.Oxidative medicine and cellular longevity · 2019Article
- Determination ofDisease markers · 2019Article
- Small ubiquitin-like modifier/sentrin-specific peptidase 1 associates with chemotherapy and is a risk factor for poor prognosis of non-small cell lung cancer.Journal of clinical laboratory analysis · 2018Article
- Effects of diphyllin as a novel V-ATPase inhibitor on TE-1 and ECA-109 cells.Oncology reports · 2018Article
- Betulinic Acid Exerts Cytotoxic Activity Against Multidrug-Resistant Tumor Cells via Targeting Autocrine Motility Factor Receptor (AMFR).Frontiers in pharmacology · 2018Article
- Association ofOncology letters · 2017Article
- Article
- Betulinyl Sulfamates as Anticancer Agents and Radiosensitizers in Human Breast Cancer Cells.International journal of molecular sciences · 2015Article
- STAT3 polymorphism and Helicobacter pylori CagA strains with higher number of EPIYA-C segments independently increase the risk of gastric cancer.BMC cancer · 2015Article
- Radiotherapy-induced plasticity of prostate cancer mobilizes stem-like non-adherent, Erk signaling-dependent cells.Cell death and differentiation · 2015Article
Corrections and comments
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Authors and funding
13 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundSignal transducer and activator of transcription 3 (STAT3) is a transcription factor that regulates various cellular processes such as cell survival, angiogenesis and proliferation. In the present study, we examined that betulinic acid (BA), a triterpene from the bark of white birch, had the inhibitory effects on hypoxia-mediated activation of STAT3 in androgen independent human prostate cancer PC-3 cells. METHODOLOGY/PRINCIPAL
findingsBA inhibited the protein expression and the transcriptional activities of hypoxia-inducible factor-1α (HIF-1α) under hypoxic condition. Consistently, BA blocked hypoxia-induced phosphorylation, DNA binding activity and nuclear accumulation of STAT3. In addition, BA significantly reduced cellular and secreted levels of vascular endothelial growth factor (VEGF), a critical angiogenic factor and a target gene of STAT3 induced under hypoxia. Furthermore, BA prevented in vitro capillary tube formation in human umbilical vein endothelial cells (HUVECs) maintained in conditioned medium of hypoxic PC-3 cells, implying anti-angiogenic activity of BA under hypoxic condition. Of note, chromatin immunoprecipitation (ChiP) assay revealed that BA inhibited binding of HIF-1α and STAT3 to VEGF promoter. Furthermore, silencing STAT3 using siRNA transfection effectively enhanced the reduced VEGF production induced by BA treatment under hypoxia. CONCLUSIONS/SIGNIFICANCE: Taken together, our results suggest that BA has anti-angiogenic activity by disturbing the binding of HIF-1α and STAT3 to the VEGF promoter in hypoxic PC-3 cells.
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