ArticlePloS one2013
Betulinic acid selectively increases protein degradation and enhances prostate cancer-specific apoptosis: possible role for inhibition of deubiquitinase activity.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers, 1 of them a synthesis that pooled it.
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Who cites it
35 citing papers in PubMed, 1 synthesis or guideline pooled it, 76 citations in OpenAlex.
- Phytochemicals in Inhibition of Prostate Cancer: Evidence from Molecular Mechanisms Studies.Biomolecules · 2022Pooled it
- Participation of MDM2 in Pro-Apoptotic and Androgen Receptor- Degrading Potency of Selected Steroid and Terpenoid Derivatives.Current medicinal chemistry · 2026Review
- Article
- Natural Products Targeting the Androgen Receptor Signaling Pathway: Therapeutic Potential and Mechanisms.Current issues in molecular biology · 2025Review
- A Novel Chemotherapy Combination to Enhance Proteotoxic Cell Death in Hepatocellular Carcinoma Experimental Models Without Killing Non-Cancer Cells.International journal of molecular sciences · 2025Article
- Betulinic acid and obesity-related disorders.Frontiers in pharmacology · 2025Review
- Anthricin-induced hyperactive proteasome and its molecular mechanism.Biochemistry and biophysics reports · 2024Article
- Ubiquitination and deubiquitination in cancer: from mechanisms to novel therapeutic approaches.Molecular cancer · 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
- Epigenetic modification regulates tumor progression and metastasis through EMT (Review).International journal of oncology · 2022Review
- Natural compounds in the regulation of proteostatic pathways: An invincible artillery against stress, ageing, and diseases.Acta pharmaceutica Sinica. B · 2021Review
- Prostate Cancer-Focus on Cholesterol.Cancers · 2021Review
- Targeting the Ubiquitin-Proteasome System for Cancer Therapeutics by Small-Molecule Inhibitors.Cancers · 2021Review
- Regulation of Cancer Metabolism by Deubiquitinating Enzymes: The Warburg Effect.International journal of molecular sciences · 2021Review
- Anti-Cancer and Immunomodulatory Activity of a Polyethylene Glycol-Betulinic Acid Conjugate on Pancreatic Cancer Cells.Life (Basel, Switzerland) · 2021Article
- Bioassay-Guided Identification of the Antiproliferative Compounds ofMolecules (Basel, Switzerland) · 2021Article
- Natural Product-Based Studies for the Management of Castration-Resistant Prostate Cancer: Computational to Clinical Studies.Frontiers in pharmacology · 2021Review
- Prostate cancer: Therapeutic prospect with herbal medicine.Current research in pharmacology and drug discovery · 2021Review
- Natural Products for the Management of Castration-Resistant Prostate Cancer: Special Focus on Nanoparticles Based Studies.Frontiers in cell and developmental biology · 2021Review
- Advances in Deubiquitinating Enzyme Inhibition and Applications in Cancer Therapeutics.Cancers · 2020Review
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Inhibition of the ubiquitin-proteasome system (UPS) of protein degradation is a valid anti-cancer strategy and has led to the approval of bortezomib for the treatment of multiple myeloma. However, the alternative approach of enhancing the degradation of oncoproteins that are frequently overexpressed in cancers is less developed. Betulinic acid (BA) is a plant-derived small molecule that can increase apoptosis specifically in cancer but not in normal cells, making it an attractive anti-cancer agent. Our results in prostate cancer suggested that BA inhibited multiple deubiquitinases (DUBs), which resulted in the accumulation of poly-ubiquitinated proteins, decreased levels of oncoproteins, and increased apoptotic cell death. In normal fibroblasts, however, BA did not inhibit DUB activity nor increased total poly-ubiquitinated proteins, which was associated with a lack of effect on cell death. In the TRAMP transgenic mouse model of prostate cancer, treatment with BA (10 mg/kg) inhibited primary tumors, increased apoptosis, decreased angiogenesis and proliferation, and lowered androgen receptor and cyclin D1 protein. BA treatment also inhibited DUB activity and increased ubiquitinated proteins in TRAMP prostate cancer but had no effect on apoptosis or ubiquitination in normal mouse tissues. Overall, our data suggests that BA-mediated inhibition of DUBs and induction of apoptotic cell death specifically in prostate cancer but not in normal cells and tissues may provide an effective non-toxic and clinically selective agent for chemotherapy.
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Registered trials
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