ArticleJournal of experimental & clinical cancer research : CR2013
A fluorescent curcumin-based Zn(II)-complex reactivates mutant (R175H and R273H) p53 in cancer cells.
Article in Journal of experimental & clinical cancer research : CR, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
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Who cites it
44 citing papers in PubMed, 77 citations in OpenAlex.
- The deubiquitinase inhibitor WP1130 drives nuclear aggregation and reactivation of mutant p53 for selective cancer cell targeting.The FEBS journal · 2025Article
- Manipulating the cGAS-STING Axis: advancing innovative strategies for osteosarcoma therapeutics.Frontiers in immunology · 2025Review
- From regulation to deregulation of p53 in hematologic malignancies: implications for diagnosis, prognosis and therapy.Biomarker research · 2024Review
- Recent Advances on Mutant p53: Unveiling Novel Oncogenic Roles, Degradation Pathways, and Therapeutic Interventions.Biomolecules · 2024Review
- Nanoscale Metal-Organic Frameworks-Mediated Degradation of Mutant p53 Proteins and Activation of cGAS-STING Pathway for Enhanced Cancer Immunotherapy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Cell fate regulation governed by p53: Friends or reversible foes in cancer therapy.Cancer communications (London, England) · 2024Review
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- OPUS-Mut: Studying the Effect of Protein Mutation through Side-Chain Modeling.Journal of chemical theory and computation · 2023Article
- UBE2T promotes glioblastoma malignancy through ubiquitination-mediated degradation of RPL6.Cancer science · 2023Article
- The Challenges and Prospects of p53-Based Therapies in Ovarian Cancer.Biomolecules · 2023Review
- Targeting mutant p53 stabilization for cancer therapy.Frontiers in pharmacology · 2023Review
- Transition of amyloid/mutant p53 from tumor suppressor to an oncogene and therapeutic approaches to ameliorate metastasis and cancer stemness.Cancer cell international · 2022Review
- Anticancer Therapeutic Strategies Targeting p53 Aggregation.International journal of molecular sciences · 2022Review
- A role for bioinorganic chemistry in the reactivation of mutant p53 in cancer.Journal of biological inorganic chemistry : JBIC : a publication of the Society of Biological Inorganic Chemistry · 2022Review
- Zinc-doped Prussian blue nanoparticles for mutp53-carrying tumor ion interference and photothermal therapy.Asian journal of pharmaceutical sciences · 2022Article
- P53 protein and the diseases in central nervous system.Frontiers in genetics · 2022Review
- Tumor suppressor p53: Biology, signaling pathways, and therapeutic targeting.Biochimica et biophysica acta. Reviews on cancer · 2021Review
- Metal-Curcumin Complexes in Therapeutics: An Approach to Enhance Pharmacological Effects of Curcumin.International journal of molecular sciences · 2021Review
- Mutant p53s and chromosome 19 microRNA cluster overexpression regulate cancer testis antigen expression and cellular transformation in hepatocellular carcinoma.Scientific reports · 2021Article
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 3 countries.
Funding
Abstract
backgroundMutations of the p53 oncosuppressor gene are amongst the most frequent aberration seen in human cancer. Some mutant (mt) p53 proteins are prone to loss of Zn(II) ion that is bound to the wild-type (wt) core, promoting protein aggregation and therefore unfolding. Misfolded p53 protein conformation impairs wtp53-DNA binding and transactivation activities, favouring tumor growth and resistance to antitumor therapies. Screening studies, devoted to identify small molecules that reactivate mtp53, represent therefore an attractive anti-cancer therapeutic strategy. Here we tested a novel fluorescent curcumin-based Zn(II)-complex (Zn-curc) to evaluate its effect on mtp53 reactivation in cancer cells.
methodsP53 protein conformation was examined after Zn-curc treatment by immunoprecipitation and immunofluorescence assays, using conformation-specific antibodies. The mtp53 reactivation was evaluated by chromatin-immunoprecipitation (ChIP) and semi-quantitative RT-PCR analyses of wild-type p53 target genes. The intratumoral Zn-curc localization was evaluated by immunofluorescence analysis of glioblastoma tissues of an ortothopic mice model.
resultsThe Zn-curc complex induced conformational change in p53-R175H and -R273H mutant proteins, two of the most common p53 mutations. Zn-curc treatment restored wtp53-DNA binding and transactivation functions and induced apoptotic cell death. In vivo studies showed that the Zn-curc complex reached glioblastoma tissues of an ortothopic mice model, highlighting its ability to crossed the blood-tumor barrier.
conclusionsOur results demonstrate that Zn-curc complex may reactivate specific mtp53 proteins and that may cross the blood-tumor barrier, becoming a promising compound for the development of drugs to halt tumor growth.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.