ArticleMolecules (Basel, Switzerland)2019
Benzimidazoles Downregulate Mdm2 and MdmX and Activate p53 in MdmX Overexpressing Tumor Cells.
Article in Molecules (Basel, Switzerland), 2019. 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, 31 citations in OpenAlex.
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- Transcriptome analysis reveals the anticancer effects of fenbendazole on ovarian cancer: an in vitro and in vivo study.BMC cancer · 2024Article
- Long-Read MDM4 Sequencing Reveals Aberrant Isoform Landscape in Metastatic Melanomas.International journal of molecular sciences · 2024Article
- Preparation and evaluation of fenbendazole methyl-β-cyclodextrin inclusion complexes.BMC veterinary research · 2024Article
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- Anti-cancer effect of fenbendazole-incorporated PLGA nanoparticles in ovarian cancer.Journal of gynecologic oncology · 2023Article
- Benzimidazole and its derivatives as cancer therapeutics: The potential role from traditional to precision medicine.Acta pharmaceutica Sinica. B · 2023Review
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- Anti-cancer effects of fenbendazole on 5-fluorouracil-resistant colorectal cancer cells.The Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology · 2022Article
- Synthesis and Biological Evaluation of Novel Synthetic Indolone Derivatives as Anti-Tumor Agents Targeting p53-MDM2 and p53-MDMX.Molecules (Basel, Switzerland) · 2022Article
- β-Lactoglobulin-Modified Mesoporous Silica Nanoparticles: A Promising Carrier for the Targeted Delivery of Fenbendazole into Prostate Cancer Cells.Pharmaceutics · 2022Article
- PEGylated Mesoporous Silica Nanoparticles (MCM-41): A Promising Carrier for the Targeted Delivery of Fenbendazole into Prostrate Cancer Cells.Pharmaceutics · 2021Article
- Low-Dose Albendazole Inhibits Epithelial-Mesenchymal Transition of Melanoma Cells by Enhancing Phosphorylated GSK-3Journal of oncology · 2021Article
- CDK9 activity is critical for maintaining MDM4 overexpression in tumor cells.Cell death & disease · 2020Article
- The Antitumor Potentials of Benzimidazole Anthelmintics as Repurposing Drugs.Immune network · 2020Review
- Anti-Cancer Activity of a 5-Aminopyrazole Derivative Lead Compound (BC-7) and Potential Synergistic Cytotoxicity with Cisplatin against Human Cervical Cancer Cells.International journal of molecular sciences · 2019Article
- Bioactive Molecules and Their Mechanisms of Action.Molecules (Basel, Switzerland) · 2019Article
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Tumor suppressor p53 is mutated in about 50% of cancers. Most malignant melanomas carry wild-type p53, but p53 activity is often inhibited due to overexpression of its negative regulators Mdm2 or MdmX. We performed high throughput screening of 2448 compounds on A375 cells carrying p53 activity luciferase reporter construct to reveal compounds that promote p53 activity in melanoma. Albendazole and fenbendazole, two approved and commonly used benzimidazole anthelmintics, stimulated p53 activity and were selected for further studies. The protein levels of p53 and p21 increased upon the treatment with albendazole and fenbendazole, indicating activation of the p53-p21 pathway, while the levels of Mdm2 and MdmX decreased in melanoma and breast cancer cells overexpressing these proteins. We also observed a reduction of cell viability and changes of cellular morphology corresponding to mitotic catastrophe, i.e., G2/M cell cycle arrest of large multinucleated cells with disrupted microtubules. In summary, we established a new tool for testing the impact of small molecule compounds on the activity of p53 and used it to identify the action of benzimidazoles in melanoma cells. The drugs promoted the stability and transcriptional activity of wild-type p53 via downregulation of its negative regulators Mdm2 and MdmX in cells overexpressing these proteins. The results indicate the potential for repurposing the benzimidazole anthelmintics for the treatment of cancers overexpressing p53 negative regulators.
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