ArticleMolecular oncology2016
MDM2 antagonist nutlin-3a sensitizes tumors to V-ATPase inhibition.
Article in Molecular oncology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 18 citations in OpenAlex.
- Anticancer Compounds from Myxobacteria: Current Scenario and Future Perspectives.Anti-cancer agents in medicinal chemistry · 2026Review
- Metabolic Roles of HIF1, c-Myc, and p53 in Glioma Cells.Metabolites · 2024Review
- MDM2 inhibitors-mediated disruption of mitochondrial metabolism: A novel therapeutic strategy for retinoblastoma.Frontiers in oncology · 2022Review
- Design and Synthesis of Simplified Polyketide Analogs: New Modalities beyond the Rule of 5.ChemMedChem · 2021Review
- MDM2/X Inhibitors as Radiosensitizers for Glioblastoma Targeted Therapy.Frontiers in oncology · 2021Review
- Design, Synthesis and Biological Evaluation of Highly Potent Simplified Archazolids.ChemMedChem · 2020Article
- Suzuki coupling-based synthesis of VATPase inhibitor archazolid natural product derived fragments.RSC advances · 2019Article
- Helping the Released Guardian: Drug Combinations for Supporting the Anticancer Activity of HDM2 (MDM2) Antagonists.Cancers · 2019Review
- MDM2 Integrates Cellular Respiration and Apoptotic Signaling through NDUFS1 and the Mitochondrial Network.Molecular cell · 2019Article
- Review
- Synthesis of a CSynlett : accounts and rapid communications in synthetic organic chemistry · 2017Article
- TIGAR knockdown radiosensitizes TrxR1-overexpressing glioma in vitro and in vivo via inhibiting Trx1 nuclear transport.Scientific reports · 2017Article
- Total syntheses of the archazolids: an emerging class of novel anticancer drugs.Beilstein journal of organic chemistry · 2017Review
- MDM2 antagonist nutlin-3a sensitizes tumors to V-ATPase inhibition.Molecular oncology · 2016Article
Corrections and comments
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Authors and funding
6 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Treating cancer is one of the big challenges of this century and it has become evident that single chemotherapeutic treatment is rarely effective. As tumors often carry multiple mutations using combination therapy which addresses different targets seems therefore more beneficial. One of the most frequently mutated genes in tumors is the tumor suppressor p53. Significant work has been put in the development of p53 activators, which are now in clinical studies against diverse cancers. Recently, we could show that inhibition of V-ATPase, a multisubunit proton pump, by archazolid induces p53 protein levels in cancer cells. In this study, we provide evidence that the combination of archazolid with the p53 activator nutlin-3a is synergistically inducing cell death in different p53 wild type tumor cell lines. Mechanistically, this effect could presumably be attributed to reduction of glycolysis as TIGAR mRNA levels were increased and glucose uptake and Glut1 protein levels were reduced. In addition, combination treatment highly activated pro-apoptotic pathways including IGFBP3 and Bax inducing caspase-9 and PARP cleavage. Remarkably, combination of archazolid and nutlin-3a was more efficient in reducing tumor growth compared to single dose treatment in a U87MG mouse model in vivo. Hence, our findings suggest the combination of archazolid and nutlin-3a as a highly promising strategy for the treatment of p53 wild type tumors.
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