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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...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2016
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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. |
format | Online Article Text |
id | pubmed-5058503 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
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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