ArticleBMC cancer2011
Betulinic acid inhibits colon cancer cell and tumor growth and induces proteasome-dependent and -independent downregulation of specificity proteins (Sp) transcription factors.
Article in BMC cancer, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 68 papers, 1 of them a synthesis that pooled it.
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Who cites it
68 citing papers in PubMed, 1 synthesis or guideline pooled it, 162 citations in OpenAlex.
- Pre-mir-27a rs895819 polymorphism and cancer risk: a meta-analysis.Molecular biology reports · 2013Pooled it
- Targeting phosphofructokinase in cancer: integrating natural products for metabolic reprogramming and therapeutic innovation.Frontiers in pharmacology · 2026Review
- Investigating the Epigenetic Therapeutic Potential of Natural Compounds in Cancer.International journal of molecular sciences · 2025Review
- Betulinic Acid ω-Triphenylphosphonium Alkyl Esters: Antiproliferative Activities and In Silico Pharmacokinetic Profiles.Biomedicines · 2025Article
- Enhanced ZBTB10 expression induced by betulinic acid inhibits gastric cancer progression by inactivating the ARRDC3/ITGB4/PI3K/AKT pathway.Cellular oncology (Dordrecht, Netherlands) · 2025Article
- Polyphenol Intake in Elderly Patients: A Novel Approach to Counteract Colorectal Cancer Risk?International journal of molecular sciences · 2025Review
- Betulinic acid and obesity-related disorders.Frontiers in pharmacology · 2025Review
- FNDC5 inhibits autophagy of bone marrow mesenchymal stem cells and promotes their survival after transplantation by downregulating Sp1.Cell death discovery · 2023Article
- Connection between Radiation-Regulating Functions of Natural Products and miRNAs Targeting Radiomodulation and Exosome Biogenesis.International journal of molecular sciences · 2023Review
- Quercetin's Dual Mode of Action to Counteract the Sp1-miR-27a Axis in Colorectal Cancer Cells.Antioxidants (Basel, Switzerland) · 2023Article
- Targeting Transcription Factor YY1 for Cancer Treatment: Current Strategies and Future Directions.Cancers · 2023Review
- Specificity Proteins (Sp) and Cancer.International journal of molecular sciences · 2023Review
- 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
- Targeting transforming growth factor-β signalling for cancer prevention and intervention: Recent advances in developing small molecules of natural origin.Clinical and translational medicine · 2022Review
- Caspase-Mediated Cleavage of the Transcription Factor Sp3: Possible Relevance to Cancer and the Lytic Cycle of Kaposi's Sarcoma-Associated Herpesvirus.Microbiology spectrum · 2022Article
- Mechanism of ferroptosis in traditional chinese medicine for clinical treatment: A review.Frontiers in pharmacology · 2022Review
- Antitumorigenic effect of insect-derived peptide poecilocorisin-1 in human skin cancer cells through regulation of Sp1 transcription factor.Scientific reports · 2021Article
- A Review on Preparation of Betulinic Acid and Its Biological Activities.Molecules (Basel, Switzerland) · 2021Review
- Regulation of Cancer Metabolism by Deubiquitinating Enzymes: The Warburg Effect.International journal of molecular sciences · 2021Review
- Natural Products in the Prevention of Metabolic Diseases: Lessons Learned from the 20th KAST Frontier Scientists Workshop.Nutrients · 2021Review
8 more citing papers are in PubMed but not listed here.
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Authors and funding
5 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundBetulinic acid (BA) inhibits growth of several cancer cell lines and tumors and the effects of BA have been attributed to its mitochondriotoxicity and inhibition of multiple pro-oncogenic factors. Previous studies show that BA induces proteasome-dependent degradation of specificity protein (Sp) transcription factors Sp1, Sp3 and Sp4 in prostate cancer cells and this study focused on the mechanism of action of BA in colon cancer cells.
methodsThe effects of BA on colon cancer cell proliferation and apoptosis and tumor growth in vivo were determined using standardized assays. The effects of BA on Sp proteins and Sp-regulated gene products were analyzed by western blots, and real time PCR was used to determine microRNA-27a (miR-27a) and ZBTB10 mRNA expression.
resultsBA inhibited growth and induced apoptosis in RKO and SW480 colon cancer cells and inhibited tumor growth in athymic nude mice bearing RKO cells as xenograft. BA also decreased expression of Sp1, Sp3 and Sp4 transcription factors which are overexpressed in colon cancer cells and decreased levels of several Sp-regulated genes including survivin, vascular endothelial growth factor, p65 sub-unit of NFκB, epidermal growth factor receptor, cyclin D1, and pituitary tumor transforming gene-1. The mechanism of action of BA was dependent on cell context, since BA induced proteasome-dependent and proteasome-independent downregulation of Sp1, Sp3 and Sp4 in SW480 and RKO cells, respectively. In RKO cells, the mechanism of BA-induced repression of Sp1, Sp3 and Sp4 was due to induction of reactive oxygen species (ROS), ROS-mediated repression of microRNA-27a, and induction of the Sp repressor gene ZBTB10.
conclusionsThese results suggest that the anticancer activity of BA in colon cancer cells is due, in part, to downregulation of Sp1, Sp3 and Sp4 transcription factors; however, the mechanism of this response is cell context-dependent.
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