ArticleJournal of experimental & clinical cancer research : CR2015
The beneficial effect of Zinc(II) on low-dose chemotherapeutic sensitivity involves p53 activation in wild-type p53-carrying colorectal cancer cells.
Article in Journal of experimental & clinical cancer research : CR, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
27 citing papers in PubMed, 41 citations in OpenAlex.
- Unveiling the prognostic and therapeutic landscape of the zinc transporter protein SLC39A family in colorectal cancer through multi-omics and machine learning approaches.Clinical and experimental medicine · 2026Article
- Metal Ions Within the Neuro-Immune-Tumor Axis.Journal of immunology research · 2026Review
- Discovery of Drugs Targeting Mutant p53 and Progress in Nano-Enabled Therapeutic Strategy for p53-Mutated Cancers.Biomolecules · 2025Review
- Zinc, copper, copper-to-zinc ratio, and other biometals in blood serum and tumor tissue of patients with colorectal cancer.Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine · 2025Article
- Combined KRAS and TP53 mutation in patients with colorectal cancer enhance chemoresistance to promote postoperative recurrence and metastasis.BMC cancer · 2024Article
- Repurposed AT9283 triggers anti-tumoral effects by targeting MKK3 oncogenic functions in Colorectal Cancer.Journal of experimental & clinical cancer research : CR · 2024Article
- Phage libraries screening on P53: Yield improvement by zinc and a new parasites-integrating analysis.PloS one · 2024Article
- Zinc Acts Synergistically with Berberine for Enhancing Its Efficacy as an Anti-cancer Agent by Inducing Clusterin-Dependent Apoptosis in HT-29 Colorectal Cancer Cells.Biological trace element research · 2023Article
- Review
- Multi-level characteristics recognition of cancer core therapeutic targets and drug screening for a broader patient population.Frontiers in pharmacology · 2023Article
- The Impact of NRF2 Inhibition on Drug-Induced Colon Cancer Cell Death and p53 Activity: A Pilot Study.Biomolecules · 2022Article
- Zinc Supplementation Enhances the Pro-Death Function of UPR in Lymphoma Cells Exposed to Radiation.Biology · 2022Article
- P62/SQSTM1/Keap1/NRF2 Axis Reduces Cancer Cells Death-Sensitivity in Response to Zn(II)-Curcumin Complex.Biomolecules · 2021Article
- Biological Application of a Fluorescent Zinc Sensing Probe for the Analysis of Zinc Bioavailability Using Caco-2 Cells as an In-Vitro Cellular Model.Journal of fluorescence · 2020Article
- Nephroprotective Effect ofBiomolecules · 2020Article
- A ruthenium(II)-curcumin compound modulates NRF2 expression balancing the cancer cell death/survival outcome according to p53 status.Journal of experimental & clinical cancer research : CR · 2020Article
- Interplay between Endoplasmic Reticulum (ER) Stress and Autophagy Induces Mutant p53H273 Degradation.Biomolecules · 2020Article
- Autophagy manipulation as a strategy for efficient anticancer therapies: possible consequences.Journal of experimental & clinical cancer research : CR · 2019Review
- Wild-type p53 regulates OTOP2 transcription through DNA loop alteration of the promoter in colorectal cancer.FEBS open bio · 2019Article
- p53-Dependent PUMA to DRAM antagonistic interplay as a key molecular switch in cell-fate decision in normal/high glucose conditions.Journal of experimental & clinical cancer research : CR · 2017Article
Corrections and comments
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Authors and funding
8 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundActivation of wild-type p53 in response to genotoxic stress occurs through different mechanisms including protein conformation, posttranslational modifications, and nuclear localization, leading to DNA binding to sequence-specific promoters. Zinc ion plays a crucial role in stabilizing p53/DNA binding to induce canonical target genes. Mutant p53 proteins undergo protein misfolding that can be counteracted by zinc. However, whether zinc supplementation might have a beneficial antitumor effect in wild-type p53-carrying cells in combination with drugs, has not been addressed so far.
methodsIn this study we compared the effect of two antitumor treatments: on the one hand wild-type p53-carrying colon cancer cells were treated with low and high doses of chemotherapeutic agent Adriamycin and, on the other hand, Adriamycin was used in combination with ZnCl2. Biochemical and molecular analyses were applied to evaluate p53 activity and biological outcomes in this setting. Finally, the effect of the different combination treatments were applied to assess tumor growth in vivo in tumor xenografts.
resultsWe found that low-dose Adriamycin did not induce p53 activation in wtp53-carrying colon cancer cells, unless in combination with ZnCl2. Mechanistically, ZnCl2 was a key determinant in inducing wtp53/DNA binding and transactivation of target genes in response to low-dose Adriamycin that used alone did not achieve such effects. Finally, in vivo studies, in a model of wtp53 colon cancer xenograft, show that low-dose Adriamycin did not induce tumor regression unless in combination with ZnCl2 that activated endogenous wtp53.
conclusionsThese results provide evidence that ZnCl2 might be a valuable adjuvant in chemotherapeutic regimens of colorectal cancer harboring wild-type p53, able to both activate p53 and reduce the amount of drugs for antitumor purposes.
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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.