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Direct intra-tumoral injection of zinc-acetate halts tumor growth in a xenograft model of prostate cancer

Intracellular levels of zinc have shown a strong inverse correlation to growth and malignancy of prostate cancer. To date, studies of zinc supplementation in prostate cancer have been equivocal and have not accounted for bioavailability of zinc. Therefore, we hypothesized that direct intra-tumoral i...

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Autores principales: Shah, Maulik R, Kriedt, Christopher L, Lents, Nathan H, Hoyer, Mary K, Jamaluddin, Nimah, Klein, Claudette, Baldassare, Joseph
Formato: Texto
Lenguaje:English
Publicado: BioMed Central 2009
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2701928/
https://www.ncbi.nlm.nih.gov/pubmed/19534805
http://dx.doi.org/10.1186/1756-9966-28-84
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author Shah, Maulik R
Kriedt, Christopher L
Lents, Nathan H
Hoyer, Mary K
Jamaluddin, Nimah
Klein, Claudette
Baldassare, Joseph
author_facet Shah, Maulik R
Kriedt, Christopher L
Lents, Nathan H
Hoyer, Mary K
Jamaluddin, Nimah
Klein, Claudette
Baldassare, Joseph
author_sort Shah, Maulik R
collection PubMed
description Intracellular levels of zinc have shown a strong inverse correlation to growth and malignancy of prostate cancer. To date, studies of zinc supplementation in prostate cancer have been equivocal and have not accounted for bioavailability of zinc. Therefore, we hypothesized that direct intra-tumoral injection of zinc could impact prostate cancer growth. In this study, we evaluated the cytotoxic properties of the pH neutral salt zinc acetate on the prostate cancer cell lines PC3, DU145 and LNCaP. Zinc acetate killed prostate cancer cell lines in vitro, independent of androgen sensitivity, in a dose-dependent manner in a range between 200 and 600 μM. Cell death occurred rapidly with 50% cell death by six hours and maximal cell death by 18 hours. We next established a xenograft model of prostate cancer and tested an experimental treatment protocol of direct intra-tumoral injection of zinc acetate. We found that zinc treatments halted the growth of the prostate cancer tumors and substantially extended the survival of the animals, whilst causing no detectable cytoxicity to other tissues. Thus, our studies form a solid proof-of-concept that direct intra-tumoral injection of zinc acetate could be a safe and effective treatment strategy for prostate cancer.
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spelling pubmed-27019282009-06-26 Direct intra-tumoral injection of zinc-acetate halts tumor growth in a xenograft model of prostate cancer Shah, Maulik R Kriedt, Christopher L Lents, Nathan H Hoyer, Mary K Jamaluddin, Nimah Klein, Claudette Baldassare, Joseph J Exp Clin Cancer Res Research Intracellular levels of zinc have shown a strong inverse correlation to growth and malignancy of prostate cancer. To date, studies of zinc supplementation in prostate cancer have been equivocal and have not accounted for bioavailability of zinc. Therefore, we hypothesized that direct intra-tumoral injection of zinc could impact prostate cancer growth. In this study, we evaluated the cytotoxic properties of the pH neutral salt zinc acetate on the prostate cancer cell lines PC3, DU145 and LNCaP. Zinc acetate killed prostate cancer cell lines in vitro, independent of androgen sensitivity, in a dose-dependent manner in a range between 200 and 600 μM. Cell death occurred rapidly with 50% cell death by six hours and maximal cell death by 18 hours. We next established a xenograft model of prostate cancer and tested an experimental treatment protocol of direct intra-tumoral injection of zinc acetate. We found that zinc treatments halted the growth of the prostate cancer tumors and substantially extended the survival of the animals, whilst causing no detectable cytoxicity to other tissues. Thus, our studies form a solid proof-of-concept that direct intra-tumoral injection of zinc acetate could be a safe and effective treatment strategy for prostate cancer. BioMed Central 2009-06-17 /pmc/articles/PMC2701928/ /pubmed/19534805 http://dx.doi.org/10.1186/1756-9966-28-84 Text en Copyright © 2009 Shah et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( (http://creativecommons.org/licenses/by/2.0) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research
Shah, Maulik R
Kriedt, Christopher L
Lents, Nathan H
Hoyer, Mary K
Jamaluddin, Nimah
Klein, Claudette
Baldassare, Joseph
Direct intra-tumoral injection of zinc-acetate halts tumor growth in a xenograft model of prostate cancer
title Direct intra-tumoral injection of zinc-acetate halts tumor growth in a xenograft model of prostate cancer
title_full Direct intra-tumoral injection of zinc-acetate halts tumor growth in a xenograft model of prostate cancer
title_fullStr Direct intra-tumoral injection of zinc-acetate halts tumor growth in a xenograft model of prostate cancer
title_full_unstemmed Direct intra-tumoral injection of zinc-acetate halts tumor growth in a xenograft model of prostate cancer
title_short Direct intra-tumoral injection of zinc-acetate halts tumor growth in a xenograft model of prostate cancer
title_sort direct intra-tumoral injection of zinc-acetate halts tumor growth in a xenograft model of prostate cancer
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2701928/
https://www.ncbi.nlm.nih.gov/pubmed/19534805
http://dx.doi.org/10.1186/1756-9966-28-84
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