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The Zinc-Schiff Base-Novicidin Complex as a Potential Prostate Cancer Therapy
V. Milosavljevic, Y. Haddad, MA. Merlos Rodrigo, A. Moulick, H. Polanska, D. Hynek, Z. Heger, P. Kopel, V. Adam,
Language English Country United States
Document type Journal Article
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- MeSH
- Antineoplastic Agents chemistry pharmacology therapeutic use MeSH
- Apoptosis drug effects MeSH
- Gene Expression drug effects MeSH
- Microscopy, Fluorescence MeSH
- Caspase 1 metabolism MeSH
- Antimicrobial Cationic Peptides chemistry MeSH
- Coordination Complexes chemistry pharmacology therapeutic use MeSH
- Humans MeSH
- Molecular Conformation MeSH
- Cell Line, Tumor MeSH
- Prostatic Neoplasms drug therapy MeSH
- Cation Transport Proteins metabolism MeSH
- Schiff Bases chemistry MeSH
- Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization MeSH
- Zinc chemistry metabolism MeSH
- Check Tag
- Humans MeSH
- Male MeSH
- Publication type
- Journal Article MeSH
Prostate cancer cells control energy metabolism by chelating intracellular zinc. Thus, zinc delivery has been a popular therapeutic approach for prostate cancer. Here, we propose the use of the membrane-penetrating peptide Novicidin connected to zinc-Schiff base as a carrier vehicle for the delivery of zinc to prostate cells. Mass spectrometry, electrochemistry and spectrophotometry confirmed the formation/stability of this complex and provided insight regarding the availability of zinc for complex interactions. This delivery system showed minor toxicity in normal PNT1A cells and high potency towards PC3 tumor cells. The complex preferentially penetrated PC3 tumor cells in contrast to confinement to the membranes of PNT1A. Furthermore, zinc uptake was confirmed in both cell lines. Molecular analysis was used to confirm the activation of zinc stress (e.g., ZnT-1) and apoptosis (e.g., CASP-1). Our results strongly suggest that the zinc-Schiff base-Novicidin complex has great potential as a novel anticancer drug.
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