title: The Zinc-Schiff Base-Novicidin Complex as a Potential Prostate Cancer Therapy.
abstract: 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.
authors.affiliation: Department of Chemistry and Biochemistry, Mendel University in Brno, Zemedelska 1, CZ-613 00, Brno, Czech Republic, European Union.
authors.forename: Vedran
authors.initials: V
authors.lastname: Milosavljevic
authors.affiliation: Department of Chemistry and Biochemistry, Mendel University in Brno, Zemedelska 1, CZ-613 00, Brno, Czech Republic, European Union.
authors.forename: Yazan
authors.initials: Y
authors.lastname: Haddad
authors.affiliation: Department of Chemistry and Biochemistry, Mendel University in Brno, Zemedelska 1, CZ-613 00, Brno, Czech Republic, European Union.|Central European Institute of Technology, Brno University of Technology, Purkynova 123, CZ-612 00, Brno, Czech Republic, European Union.
authors.forename: Miguel Angel
authors.initials: MA
authors.lastname: Merlos Rodrigo
authors.affiliation: Central European Institute of Technology, Brno University of Technology, Purkynova 123, CZ-612 00, Brno, Czech Republic, European Union.
authors.forename: Amitava
authors.initials: A
authors.lastname: Moulick
authors.affiliation: Department of Physiology, Faculty of Medicine, Masaryk University, Kamenice 5, CZ-625 00, Brno, Czech Republic, European Union.
authors.forename: Hana
authors.initials: H
authors.lastname: Polanska
authors.affiliation: Department of Chemistry and Biochemistry, Mendel University in Brno, Zemedelska 1, CZ-613 00, Brno, Czech Republic, European Union.|Central European Institute of Technology, Brno University of Technology, Purkynova 123, CZ-612 00, Brno, Czech Republic, European Union.
authors.forename: David
authors.initials: D
authors.lastname: Hynek
authors.affiliation: Department of Chemistry and Biochemistry, Mendel University in Brno, Zemedelska 1, CZ-613 00, Brno, Czech Republic, European Union.|Central European Institute of Technology, Brno University of Technology, Purkynova 123, CZ-612 00, Brno, Czech Republic, European Union.
authors.forename: Zbynek
authors.initials: Z
authors.lastname: Heger
authors.affiliation: Department of Chemistry and Biochemistry, Mendel University in Brno, Zemedelska 1, CZ-613 00, Brno, Czech Republic, European Union.|Central European Institute of Technology, Brno University of Technology, Purkynova 123, CZ-612 00, Brno, Czech Republic, European Union.
authors.forename: Pavel
authors.initials: P
authors.lastname: Kopel
authors.affiliation: Department of Chemistry and Biochemistry, Mendel University in Brno, Zemedelska 1, CZ-613 00, Brno, Czech Republic, European Union.|Central European Institute of Technology, Brno University of Technology, Purkynova 123, CZ-612 00, Brno, Czech Republic, European Union.
authors.forename: Vojtech
authors.initials: V
authors.lastname: Adam
mesh_terms: D023181:Antimicrobial Cationic Peptides / Q000737:chemistry*; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D020170:Caspase 1 / Q000378:metabolism; D027682:Cation Transport Proteins / Q000378:metabolism; D045744:Cell Line, Tumor; D056831:Coordination Complexes / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D008297:Male; D008856:Microscopy, Fluorescence; D008968:Molecular Conformation; D011471:Prostatic Neoplasms / Q000188:drug therapy; D012545:Schiff Bases / Q000737:chemistry*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D015032:Zinc / Q000737:chemistry* / Q000378:metabolism
chemical_list: D023181:Antimicrobial Cationic Peptides; D000970:Antineoplastic Agents; D027682:Cation Transport Proteins; D056831:Coordination Complexes; C498299:SLC30A1 protein, human; D012545:Schiff Bases; C554278:novicidin; D020170:Caspase 1; D015032:Zinc