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The Zinc-Schiff Base-Novicidin Complex as a Potential Prostate Cancer Therapy

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...

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Autores principales: Milosavljevic, Vedran, Haddad, Yazan, Merlos Rodrigo, Miguel Angel, Moulick, Amitava, Polanska, Hana, Hynek, David, Heger, Zbynek, Kopel, Pavel, Adam, Vojtech
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5058503/
https://www.ncbi.nlm.nih.gov/pubmed/27727290
http://dx.doi.org/10.1371/journal.pone.0163983
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author Milosavljevic, Vedran
Haddad, Yazan
Merlos Rodrigo, Miguel Angel
Moulick, Amitava
Polanska, Hana
Hynek, David
Heger, Zbynek
Kopel, Pavel
Adam, Vojtech
author_facet Milosavljevic, Vedran
Haddad, Yazan
Merlos Rodrigo, Miguel Angel
Moulick, Amitava
Polanska, Hana
Hynek, David
Heger, Zbynek
Kopel, Pavel
Adam, Vojtech
author_sort Milosavljevic, Vedran
collection PubMed
description 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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spelling pubmed-50585032016-10-27 The Zinc-Schiff Base-Novicidin Complex as a Potential Prostate Cancer Therapy Milosavljevic, Vedran Haddad, Yazan Merlos Rodrigo, Miguel Angel Moulick, Amitava Polanska, Hana Hynek, David Heger, Zbynek Kopel, Pavel Adam, Vojtech PLoS One Research Article 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. Public Library of Science 2016-10-11 /pmc/articles/PMC5058503/ /pubmed/27727290 http://dx.doi.org/10.1371/journal.pone.0163983 Text en © 2016 Milosavljevic et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Milosavljevic, Vedran
Haddad, Yazan
Merlos Rodrigo, Miguel Angel
Moulick, Amitava
Polanska, Hana
Hynek, David
Heger, Zbynek
Kopel, Pavel
Adam, Vojtech
The Zinc-Schiff Base-Novicidin Complex as a Potential Prostate Cancer Therapy
title The Zinc-Schiff Base-Novicidin Complex as a Potential Prostate Cancer Therapy
title_full The Zinc-Schiff Base-Novicidin Complex as a Potential Prostate Cancer Therapy
title_fullStr The Zinc-Schiff Base-Novicidin Complex as a Potential Prostate Cancer Therapy
title_full_unstemmed The Zinc-Schiff Base-Novicidin Complex as a Potential Prostate Cancer Therapy
title_short The Zinc-Schiff Base-Novicidin Complex as a Potential Prostate Cancer Therapy
title_sort zinc-schiff base-novicidin complex as a potential prostate cancer therapy
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5058503/
https://www.ncbi.nlm.nih.gov/pubmed/27727290
http://dx.doi.org/10.1371/journal.pone.0163983
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