ArticleRadiation oncology (London, England)2011
Increased betulinic acid induced cytotoxicity and radiosensitivity in glioma cells under hypoxic conditions.
Article in Radiation oncology (London, England), 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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17 citing papers in PubMed, 49 citations in OpenAlex.
- Radiosensitizers in Cancer Therapy: A Global Bibliometric Analysis.bioRxiv : the preprint server for biology · 2025Article
- Betulinic acid and obesity-related disorders.Frontiers in pharmacology · 2025Review
- Zinc Influences the Efficacy of Betulinic Acid Treatment and Radiotherapy in Breast Cancer Cells.Antioxidants (Basel, Switzerland) · 2024Article
- SESN2 Knockdown Increases Betulinic Acid-Induced Radiosensitivity of Hypoxic Breast Cancer Cells.Cells · 2022Article
- Phytochemicals: Potential Therapeutic Modulators of Radiation Induced Signaling Pathways.Antioxidants (Basel, Switzerland) · 2021Review
- Betulin Sulfonamides as Carbonic Anhydrase Inhibitors and Anticancer Agents in Breast Cancer Cells.International journal of molecular sciences · 2021Article
- Review
- Natural radioprotectors and their impact on cancer drug discovery.Radiation oncology journal · 2018Article
- Anti-Trichomonas vaginalis activity of ursolic acid derivative: a promising alternative.Parasitology research · 2018Article
- Betulinic Acid Induces Apoptosis in Differentiated PC12 Cells Via ROS-Mediated Mitochondrial Pathway.Neurochemical research · 2017Article
- South Asian Medicinal Compounds as Modulators of Resistance to Chemotherapy and Radiotherapy.Cancers · 2016Review
- Betulinyl Sulfamates as Anticancer Agents and Radiosensitizers in Human Breast Cancer Cells.International journal of molecular sciences · 2015Article
- Betulinic acid derivatives NVX-207 and B10 for treatment of glioblastoma--an in vitro study of cytotoxicity and radiosensitization.International journal of molecular sciences · 2014Article
- Anti-Trichomonas vaginalis activity from triterpenoid derivatives.Parasitology research · 2014Article
- Approaches to improve the oral bioavailability and effects of novel anticancer drugs berberine and betulinic acid.PloS one · 2014Article
- The efficacy of betulinic acid in triple-negative breast cancer.SAGE open medicine · 2014Article
- The prospective role of plant products in radiotherapy of cancer: a current overview.Frontiers in pharmacology · 2011Article
Corrections and comments
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Authors and funding
11 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundBetulinic acid (BA) is a novel antineoplastic agent under evaluation for tumor therapy. Because of the selective cytotoxic effects of BA in tumor cells (including gliomas), the combination of this agent with conservative therapies (such as radiotherapy and chemotherapy) may be useful. Previously, the combination of BA with irradiation under hypoxic conditions had never been studied.
methodsIn this study, the effects of 3 to 30 μM BA on cytotoxicity, migration, the protein expression of PARP, survivin and HIF-1α, as well as radiosensitivity under normoxic and hypoxic conditions were analyzed in the human malignant glioma cell lines U251MG and U343MG. Cytotoxicity and radiosensitivity were analyzed with clonogenic survival assays, migration was analyzed with Boyden chamber assays (or scratch assays) and protein expression was examined with Western blot analyses.
resultsUnder normoxic conditions, a half maximal inhibitory concentration (IC50) of 23 μM was observed in U251MG cells and 24 μM was observed in U343MG cells. Under hypoxic conditions, 10 μM or 15 μM of BA showed a significantly increased cytotoxicity in U251MG cells (p = 0.004 and p = 0.01, respectively) and U343MG cells (p < 0.05 and p = 0.01, respectively). The combination of BA with radiotherapy resulted in an additive effect in the U343MG cell line under normoxic and hypoxic conditions. Weak radiation enhancement was observed in U251MG cell line after treatment with BA under normoxic conditions. Furthermore, under hypoxic conditions, the incubation with BA resulted in increased radiation enhancement. The enhancement factor, at an irradiation dose of 15 Gy after treatment with 10 or 15 μM BA, was 2.20 (p = 0.02) and 4.50 (p = 0.03), respectively. Incubation with BA led to decreased cell migration, cleavage of PARP and decreased expression levels of survivin in both cell lines. Additionally, BA treatment resulted in a reduction of HIF-1α protein under hypoxic conditions.
conclusionOur results suggest that BA is capable of improving the effects of tumor therapy in human malignant glioma cells, particularly under hypoxic conditions. Further investigations are necessary to characterize its potential as a radiosensitizer.
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