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.

Central European Institute of Technology Brno University of Technology Purkynova 123 CZ 612 00 Brno Czech Republic European Union

Department of Chemistry and Biochemistry Mendel University in Brno Zemedelska 1 CZ 613 00 Brno Czech Republic European Union

Department of Physiology Faculty of Medicine Masaryk University Kamenice 5 CZ 625 00 Brno Czech Republic European Union

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PLoS One. 2018 Sep 17;13(9):e0204441. doi: 10.1371/journal.pone.0204441. PubMed

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PLoS One. 2022 Jun 24;17(6):e0270734. doi: 10.1371/journal.pone.0270734. PubMed

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Characterization and in vitro Analysis of Probiotic-Derived Peptides Against Multi Drug Resistance Bacterial Infections