ArticleCancer science2017
Synergistic activity of sorafenib and betulinic acid against clonogenic activity of non-small cell lung cancer cells.
Article in Cancer science, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 34 citations in OpenAlex.
- Research advances in the application of betulinic acid for anti-inflammatory and anti-tumour therapy.Chinese medicine · 2026Review
- Proteolytic Activity Inhibition in Gingival Fluid by Cysteine Protease Inhibitors Obtained from Egg White andBiomedicines · 2025Article
- The Role of Pentacyclic Triterpenoids in Non-Small Cell Lung Cancer: The Mechanisms of Action and Therapeutic Potential.Pharmaceutics · 2024Review
- Efficacy of Sorafenib-Based Therapies for Non-Small Cell Lung Cancer.Medical sciences (Basel, Switzerland) · 2024Review
- Combination of ethyl acetate fraction from Calotropis gigantea stem bark and sorafenib induces apoptosis in HepG2 cells.PloS one · 2024Article
- Antiproliferative Properties of Triterpenoids by ECIS Method-A New Promising Approach in Anticancer Studies?Molecules (Basel, Switzerland) · 2022Article
- Biodegradable and Bioactive Carriers Based on Poly(betulin disuccinate-Pharmaceutics · 2022Article
- Targeting Mutant Kirsten Rat Sarcoma Viral Oncogene Homolog in Non-Small Cell Lung Cancer: Current Difficulties, Integrative Treatments and Future Perspectives.Frontiers in pharmacology · 2022Review
- Betulin Sulfonamides as Carbonic Anhydrase Inhibitors and Anticancer Agents in Breast Cancer Cells.International journal of molecular sciences · 2021Article
- Using response surface models to analyze drug combinations.Drug discovery today · 2021Review
- Combination Treatment With Inhibitors of ERK and Autophagy Enhances Antitumor Activity of Betulinic Acid in Non-small-Cell Lung CancerFrontiers in pharmacology · 2021Article
- Uncovering the Anti-Lung-Cancer Mechanisms of the Herbal Drug FDY2004 by Network Pharmacology.Evidence-based complementary and alternative medicine : eCAM · 2021Article
- Enhancing Anti-Tumor Activity of Sorafenib Mesoporous Silica Nanomatrix in Metastatic Breast Tumor and Hepatocellular Carcinoma via the Co-Administration with Flufenamic Acid.International journal of nanomedicine · 2020Article
- Yi Guan Jian, a Traditional Chinese Herbal Medicine, Alleviates Carbon Tetrachloride-Induced Liver Injury.Evidence-based complementary and alternative medicine : eCAM · 2019Article
- Article
- Berbamine Enhances the Efficacy of Gefitinib by Suppressing STAT3 Signaling in Pancreatic Cancer Cells.OncoTargets and therapy · 2019Article
- Sorafenib in Combination with Betulinic Acid Synergistically Induces Cell Cycle Arrest and Inhibits Clonogenic Activity in Pancreatic Ductal Adenocarcinoma Cells.International journal of molecular sciences · 2018Article
- Synergistic activity of sorafenib and betulinic acid against clonogenic activity of non-small cell lung cancer cells.Cancer science · 2017Article
- Combination Treatment of Sorafenib and Bufalin Induces Apoptosis in NCI-H292 Human Lung Cancer CellsIn vivo (Athens, Greece)Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The highly selective multi-targeted agent sorafenib is an inhibitor of a number of intracellular signaling kinases with anti-proliferative, anti-angiogenic and pro-apoptotic effects in various types of tumors, including human non-small cell lung cancer (NSCLC). Betulin displays a broad spectrum of biological and pharmacological properties, including anticancer and chemopreventive activity. Combination of drugs with different targets is a logical approach to overcome multilevel cross-stimulation among key signaling pathways in NSCLC progression. NSCLC cell lines, A549, H358 and A427, with different KRAS mutations, and normal human peripheral blood lymphocyte cells, were treated with sorafenib and betulinic acid alone and in combination. We examined the effect of different combined treatments on viability (MTS test), proliferation and apoptotic susceptibility based on flow cytometry, alterations in signaling pathways by western blotting and colony-forming ability. The combination of sorafenib with betulinic acid had a strong effect on the induction of apoptosis of different NSCLC cell lines. In addition, this combination was not toxic for human peripheral blood lymphocytes. Combination treatment changed the expression of proteins involved in the mitochondrial apoptosis pathway and induced apoptotic death by caspase activation. Importantly, combination treatment with low drug concentrations tremendously reduced the colony-forming ability of A549, H358 and A427 cells, as compared to both compounds alone. In this study, we showed that combination therapy with low concentrations of sorafenib and betulinic acid had the capacity to induce high levels of cell death and abolish clonogenic activity in some NSCLC cell lines regardless of KRAS mutations.
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