ArticleMolecular carcinogenesis2013
Betulinic acid decreases ER-negative breast cancer cell growth in vitro and in vivo: role of Sp transcription factors and microRNA-27a:ZBTB10.
Article in Molecular carcinogenesis, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
42 citing papers in PubMed, 104 citations in OpenAlex.
- Pentacyclic Triterpenoid Acids in the Treatment of Breast Cancer.Molecules (Basel, Switzerland) · 2026Review
- Advances and challenges in betulinic acid therapeutics and delivery systems for breast cancer prevention and treatment.RSC advances · 2025Review
- Foxh1 is a locus-specific PRC2 recruiter governing germ layer silencing.bioRxiv : the preprint server for biology · 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
- Pharmacological Significance, Medicinal Use, and Toxicity of Extracted and Isolated Compounds fromPlants (Basel, Switzerland) · 2025Review
- Endophytic fungi: A future prospect for breast cancer therapeutics and drug development.Heliyon · 2024Review
- Potent drug delivery enhancement of betulinic acid and NVX-207 into equine skin in vitro - a comparison between a novel oxygen flow-assisted transdermal application device and microemulsion gels.BMC veterinary research · 2024Article
- Targeting Transcription Factor YY1 for Cancer Treatment: Current Strategies and Future Directions.Cancers · 2023Review
- Anti-Inflammatory Activity of Compounds Derived fromMetabolites · 2023Article
- Natural Products as Anticancer Agents: Current Status and Future Perspectives.Molecules (Basel, Switzerland) · 2022Review
- Nutraceutical Role of Polyphenols and Triterpenes Present in the Extracts of Fruits and Leaves ofMolecules (Basel, Switzerland) · 2022Review
- A functional SNP rs895819 on pre-miR-27a is associated with bipolar disorder by targeting NCAM1.Communications biology · 2022Article
- Exploring the Cytotoxic Effects of the Extracts and Bioactive Triterpenoids fromACS pharmacology & translational science · 2021Article
- Anticancer Potential of Betulonic Acid Derivatives.International journal of molecular sciences · 2021Review
- MicroRNAs: Important Players in Breast Cancer Angiogenesis and Therapeutic Targets.Frontiers in molecular biosciences · 2021Review
- Targeting miRNA by Natural Products: A Novel Therapeutic Approach for Nonalcoholic Fatty Liver.Evidence-based complementary and alternative medicine : eCAM · 2021Review
- Two Worlds Colliding: The Interplay Between Natural Compounds and Non-Coding Transcripts in Cancer Therapy.Frontiers in pharmacology · 2021Review
- Glioma progression is suppressed by Naringenin and APO2L combination therapy via the activation of apoptosis in vitro and in vivo.Investigational new drugs · 2020Article
- Triple Negative Breast Cancer and Breast Epithelial Cells Differentially Reprogram Glucose and Lipid Metabolism upon Treatment with Triterpenic Acids.Biomolecules · 2020Article
- Biotechnological production of betulinic acid and derivatives and their applications.Applied microbiology and biotechnology · 2020Review
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Betulinic acid (BA), a pentacyclic triterpenoid isolated from tree bark is cytotoxic to cancer cells. There is evidence that specificity proteins (Sps), such as Sp1, Sp3, and Sp4, are overexpressed in tumors and contribute to the proliferative and angiogenic phenotype associated with cancer cells. The objective of this study was to determine the efficacy of BA in decreasing the Sps expression and underlying mechanisms. Results show that BA decreased proliferation and induced apoptosis of estrogen-receptor-negative breast cancer MDA-MB-231 cells. The BA-induced Sp1, Sp3, and Sp4 downregulation was accompanied by increased zinc finger ZBTB10 expression, a putative Sp-repressor and decreased microRNA-27a levels, a microRNA involved in the regulation of ZBTB10. Similar results were observed in MDA-MB-231 cells transfected with ZBTB10 expression plasmid. BA induced cell cycle arrest in the G2/M phase and increased Myt-1 mRNA (a microRNA-27a target gene), which causes inhibition in G2/M by phosphorylation of cdc2. The effects of BA were reversed by transient transfection with a mimic of microRNA-27a. In nude mice with xenografted MDA-MB-231 cells, tumor size and weight were significantly decreased by BA treatment. In tumor tissue, ZBTB10 mRNA was increased while mRNA and protein of Sp1, Sp3 and Sp4, as well as mRNA of vascular endothelial growth factor receptor (VEGFR), survivin and microRNA-27a were decreased by BA. In lungs of xenografted mice, human β2-microglobulin mRNA was decreased in BA-treated animals. These results show that the anticancer effects of BA are at least in part based on interactions with the microRNA-27a-ZBTB10-Sp-axis causing increased cell death.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.