ArticleThe Prostate2015
The cytotoxic and pro-apoptotic activities of the novel fluoropyrimidine F10 towards prostate cancer cells are enhanced by Zn(2+) -chelation and inhibiting the serine protease Omi/HtrA2.
Article in The Prostate, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers, 1 of them a synthesis that pooled it.
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Who cites it
8 citing papers in PubMed, 1 synthesis or guideline pooled it, 11 citations in OpenAlex.
- Comparative study of serum zinc concentrations in benign and malignant prostate disease: A Systematic Review and Meta-Analysis.Scientific reports · 2016Pooled it
- ZIF-8 nanoplatform coordinating ZnInternational journal of pharmaceutics: X · 2026Article
- Structural basis of substrate recognition and allosteric activation of the proapoptotic mitochondrial HtrA2 protease.Nature communications · 2024Article
- Lipid and Peptide-Oligonucleotide Conjugates for Therapeutic Purposes: From Simple Hybrids to Complex Multifunctional Assemblies.Pharmaceutics · 2023Review
- Oligonucleotides Carrying Nucleoside Antimetabolites as Potential Prodrugs.Current medicinal chemistry · 2023Review
- Mitochondrial Omi/HtrA2 signaling pathway is involved in neuronal apoptosis in patients with cerebral hemorrhage.American journal of translational research · 2023Article
- Effective encapsulation and biological activity of phosphorylated chemotherapeutics in calcium phosphosilicate nanoparticles for the treatment of pancreatic cancer.Nanomedicine : nanotechnology, biology, and medicine · 2017Article
- Prostate-specific membrane antigen-targeted liposomes specifically deliver the Zn(2+) chelator TPEN inducing oxidative stress in prostate cancer cells.Nanomedicine (London, England) · 2016Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
backgroundIntracellular Zn(2+) levels decrease during prostate cancer progression and agents that modulate intracellular Zn(2+) are cytotoxic to prostate cancer cells by an incompletely described mechanism. F10 is a new polymeric fluoropyrimidine drug-candidate that displays strong activity with minimal systemic toxicity in pre-clinical models of prostate cancer and other malignancies. The effects of exogenous Zn(2+) or Zn(2+) chelation for enhancing F10 cytotoxicity are investigated as is the role of Omi/HtrA2, a serine protease that promotes apoptosis in response to cellular stress.
methodsTo test the hypothesis that the pro-apoptotic effects of F10 could be enhanced by modulating intracellular Zn(2+) we investigated cell-permeable and cell-impermeable Zn(2+) chelators and exogenous Zn(2+) and evaluated cell viability and apoptosis in cellular models of castration-resistant prostate cancer (CRPC; PC3, C4-2). The role of Omi/HtrA2 for modulating apoptosis was evaluated by pharmacological inhibition and Western blotting.
resultsExogenous Zn(2+) initially reduced prostate cancer cell viability but these effects were transitory and were ineffective at enhancing F10 cytotoxicity. The cell-permeable Zn(2+) -chelator tetrakis-(2-pyridylmethl) ethylenediamine (TPEN) induced apoptosis in prostate cancer cells and enhanced the pro-apoptotic effects of F10. The pro-apoptotic effects of Zn(2+) -chelation in combination with F10 treatment were enhanced by inhibiting Omi/HtrA2 implicating this serine protease as a novel target for prostate cancer treatment.
conclusionsZn(2+) -chelation enhances the pro-apoptotic effects of F10 and may be useful for enhancing the effectiveness of F10 for treatment of advanced prostate cancer. The serine protease Omi/HtrA2 modulates Zn(2+) -dependent apoptosis in prostate cancer cells and represents a new target for treatment of CRPC. Prostate 75:360-369, 2015. © 2014 Wiley Periodicals, Inc.
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