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	Vedran Milosavljevic, Yazan Haddad, Miguel Angel Merlos Rodrigo, Amitava Moulick, Hana Polanska, David Hynek, Zbynek Heger, Pavel Kopel, Vojtech Adam
Journal	PloS one (PLoS One) Vol. 11 Issue 10 Pg. e0163983 ( 2016) ISSN: 1932-6203 [Electronic] United States
PMID	27727290 (Publication Type: Journal Article)
Chemical References	Antimicrobial Cationic Peptides Antineoplastic Agents Cation Transport Proteins Coordination Complexes SLC30A1 protein, human Schiff Bases novicidin Caspase 1 Zinc
Topics	Antimicrobial Cationic Peptides (chemistry) Antineoplastic Agents (chemistry, pharmacology, therapeutic use) Apoptosis (drug effects) Caspase 1 (metabolism) Cation Transport Proteins (metabolism) Cell Line, Tumor Coordination Complexes (chemistry, pharmacology, therapeutic use) Gene Expression (drug effects) Humans Male Microscopy, Fluorescence Molecular Conformation Prostatic Neoplasms (drug therapy) Schiff Bases (chemistry) Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization Zinc (chemistry, metabolism)

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