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The Major Heat Shock Proteins, Hsp70 and Hsp90, in 2-Methoxyestradiol-Mediated Osteosarcoma Cell Death Model

2-Methoxyestradiol is one of the natural 17β-estradiol derivatives and a potential novel anticancer agent currently being under evaluation in advanced phases of clinical trials. However, the mechanism of anticancer action of 2-methoxyestradiol has not been yet fully established. In our previous stud...

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Autores principales: Gorska-Ponikowska, Magdalena, Kuban-Jankowska, Alicja, Marino Gammazza, Antonella, Daca, Agnieszka, Wierzbicka, Justyna M., Zmijewski, Michal A., Luu, Hue H., Wozniak, Michal, Cappello, Francesco
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7014403/
https://www.ncbi.nlm.nih.gov/pubmed/31963524
http://dx.doi.org/10.3390/ijms21020616
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author Gorska-Ponikowska, Magdalena
Kuban-Jankowska, Alicja
Marino Gammazza, Antonella
Daca, Agnieszka
Wierzbicka, Justyna M.
Zmijewski, Michal A.
Luu, Hue H.
Wozniak, Michal
Cappello, Francesco
author_facet Gorska-Ponikowska, Magdalena
Kuban-Jankowska, Alicja
Marino Gammazza, Antonella
Daca, Agnieszka
Wierzbicka, Justyna M.
Zmijewski, Michal A.
Luu, Hue H.
Wozniak, Michal
Cappello, Francesco
author_sort Gorska-Ponikowska, Magdalena
collection PubMed
description 2-Methoxyestradiol is one of the natural 17β-estradiol derivatives and a potential novel anticancer agent currently being under evaluation in advanced phases of clinical trials. However, the mechanism of anticancer action of 2-methoxyestradiol has not been yet fully established. In our previous studies we have demonstrated that 2-methoxyestradiol selectively induces the expression and nuclear translocation of neuronal nitric oxide synthase in osteosarcoma 143B cells. Heat shock proteins (Hsps) are factors involved in the regulation of expression and activity of nitric oxide synthases. Herein, we chose osteosarcoma cell lines differed in metastatic potential, metastatic 143B and highly metastatic MG63.2 cells, in order to further investigate the anticancer mechanism of 2-methoxyestradiol. The current study aimed to determine the role of major heat shock proteins, Hsp90 and Hsp70 in 2-methoxyestradiol-induced osteosarcoma cell death. We focused on the implication of Hsp90 and Hsp70 in control under expression of neuronal nitric oxide synthase, localization of the enzyme, and further generation of nitro-oxidative stress. To give the insight into the role of Hsp90 in regulation of anticancer efficacy of 2-methoxyestradiol, we used geldanamycin as a potent Hsp90 inhibitor. Herein, we evidenced that inhibition of Hsp90 controls the protein expression of 2-methoxyestradiol-induced neuronal nitric oxide synthase and inhibits enzyme nuclear translocation. We propose that decreased level of neuronal nitric oxide synthase protein after a combined treatment with 2-methoxyestradiol and geldanamycin is directly associated with the accompanying upregulation of Hsp70 and downregulation of Hsp90. This interaction resulted in abrogation of anticancer efficacy of 2-methoxyestradiol by geldanamycin.
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spelling pubmed-70144032020-03-09 The Major Heat Shock Proteins, Hsp70 and Hsp90, in 2-Methoxyestradiol-Mediated Osteosarcoma Cell Death Model Gorska-Ponikowska, Magdalena Kuban-Jankowska, Alicja Marino Gammazza, Antonella Daca, Agnieszka Wierzbicka, Justyna M. Zmijewski, Michal A. Luu, Hue H. Wozniak, Michal Cappello, Francesco Int J Mol Sci Article 2-Methoxyestradiol is one of the natural 17β-estradiol derivatives and a potential novel anticancer agent currently being under evaluation in advanced phases of clinical trials. However, the mechanism of anticancer action of 2-methoxyestradiol has not been yet fully established. In our previous studies we have demonstrated that 2-methoxyestradiol selectively induces the expression and nuclear translocation of neuronal nitric oxide synthase in osteosarcoma 143B cells. Heat shock proteins (Hsps) are factors involved in the regulation of expression and activity of nitric oxide synthases. Herein, we chose osteosarcoma cell lines differed in metastatic potential, metastatic 143B and highly metastatic MG63.2 cells, in order to further investigate the anticancer mechanism of 2-methoxyestradiol. The current study aimed to determine the role of major heat shock proteins, Hsp90 and Hsp70 in 2-methoxyestradiol-induced osteosarcoma cell death. We focused on the implication of Hsp90 and Hsp70 in control under expression of neuronal nitric oxide synthase, localization of the enzyme, and further generation of nitro-oxidative stress. To give the insight into the role of Hsp90 in regulation of anticancer efficacy of 2-methoxyestradiol, we used geldanamycin as a potent Hsp90 inhibitor. Herein, we evidenced that inhibition of Hsp90 controls the protein expression of 2-methoxyestradiol-induced neuronal nitric oxide synthase and inhibits enzyme nuclear translocation. We propose that decreased level of neuronal nitric oxide synthase protein after a combined treatment with 2-methoxyestradiol and geldanamycin is directly associated with the accompanying upregulation of Hsp70 and downregulation of Hsp90. This interaction resulted in abrogation of anticancer efficacy of 2-methoxyestradiol by geldanamycin. MDPI 2020-01-17 /pmc/articles/PMC7014403/ /pubmed/31963524 http://dx.doi.org/10.3390/ijms21020616 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Gorska-Ponikowska, Magdalena
Kuban-Jankowska, Alicja
Marino Gammazza, Antonella
Daca, Agnieszka
Wierzbicka, Justyna M.
Zmijewski, Michal A.
Luu, Hue H.
Wozniak, Michal
Cappello, Francesco
The Major Heat Shock Proteins, Hsp70 and Hsp90, in 2-Methoxyestradiol-Mediated Osteosarcoma Cell Death Model
title The Major Heat Shock Proteins, Hsp70 and Hsp90, in 2-Methoxyestradiol-Mediated Osteosarcoma Cell Death Model
title_full The Major Heat Shock Proteins, Hsp70 and Hsp90, in 2-Methoxyestradiol-Mediated Osteosarcoma Cell Death Model
title_fullStr The Major Heat Shock Proteins, Hsp70 and Hsp90, in 2-Methoxyestradiol-Mediated Osteosarcoma Cell Death Model
title_full_unstemmed The Major Heat Shock Proteins, Hsp70 and Hsp90, in 2-Methoxyestradiol-Mediated Osteosarcoma Cell Death Model
title_short The Major Heat Shock Proteins, Hsp70 and Hsp90, in 2-Methoxyestradiol-Mediated Osteosarcoma Cell Death Model
title_sort major heat shock proteins, hsp70 and hsp90, in 2-methoxyestradiol-mediated osteosarcoma cell death model
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7014403/
https://www.ncbi.nlm.nih.gov/pubmed/31963524
http://dx.doi.org/10.3390/ijms21020616
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