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2-Methoxyestradiol Damages DNA in Glioblastoma Cells by Regulating nNOS and Heat Shock Proteins

Gliomas are the most prevalent primary tumors of the central nervous system (CNS), accounting for over fifty percent of all primary intracranial neoplasms. Glioblastoma (GBM) is the most prevalent form of malignant glioma and is often incurable. The main distinguishing trait of GBM is the presence o...

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Autores principales: Bastian, Paulina Emilia, Daca, Agnieszka, Płoska, Agata, Kuban-Jankowska, Alicja, Kalinowski, Leszek, Gorska-Ponikowska, Magdalena
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9598669/
https://www.ncbi.nlm.nih.gov/pubmed/36290736
http://dx.doi.org/10.3390/antiox11102013
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author Bastian, Paulina Emilia
Daca, Agnieszka
Płoska, Agata
Kuban-Jankowska, Alicja
Kalinowski, Leszek
Gorska-Ponikowska, Magdalena
author_facet Bastian, Paulina Emilia
Daca, Agnieszka
Płoska, Agata
Kuban-Jankowska, Alicja
Kalinowski, Leszek
Gorska-Ponikowska, Magdalena
author_sort Bastian, Paulina Emilia
collection PubMed
description Gliomas are the most prevalent primary tumors of the central nervous system (CNS), accounting for over fifty percent of all primary intracranial neoplasms. Glioblastoma (GBM) is the most prevalent form of malignant glioma and is often incurable. The main distinguishing trait of GBM is the presence of hypoxic regions accompanied by enhanced angiogenesis. 2-Methoxyestradiol (2-ME) is a well-established antiangiogenic and antiproliferative drug. In current clinical studies, 2-ME, known as Panzem, was examined for breast, ovarian, prostate, and multiple myeloma. The SW1088 grade III glioma cell line was treated with pharmacological and physiological doses of 2-ME. The induction of apoptosis and necrosis, oxidative stress, cell cycle arrest, and mitochondrial membrane potential were established by flow cytometry. Confocal microscopy was used to detect DNA damage. The Western blot technique determined the level of nitric oxide synthase and heat shock proteins. Here, for the first time, 2-ME is shown to induce nitro-oxidative stress with the concomitant modulation of heat shock proteins (HSPs) in the SW1088 grade III glioma cell line. Crucial therapeutic strategies for GMB should address both cell proliferation and angiogenesis, and due to the above, 2-ME seems to be a perfect candidate for GBM therapy.
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spelling pubmed-95986692022-10-27 2-Methoxyestradiol Damages DNA in Glioblastoma Cells by Regulating nNOS and Heat Shock Proteins Bastian, Paulina Emilia Daca, Agnieszka Płoska, Agata Kuban-Jankowska, Alicja Kalinowski, Leszek Gorska-Ponikowska, Magdalena Antioxidants (Basel) Article Gliomas are the most prevalent primary tumors of the central nervous system (CNS), accounting for over fifty percent of all primary intracranial neoplasms. Glioblastoma (GBM) is the most prevalent form of malignant glioma and is often incurable. The main distinguishing trait of GBM is the presence of hypoxic regions accompanied by enhanced angiogenesis. 2-Methoxyestradiol (2-ME) is a well-established antiangiogenic and antiproliferative drug. In current clinical studies, 2-ME, known as Panzem, was examined for breast, ovarian, prostate, and multiple myeloma. The SW1088 grade III glioma cell line was treated with pharmacological and physiological doses of 2-ME. The induction of apoptosis and necrosis, oxidative stress, cell cycle arrest, and mitochondrial membrane potential were established by flow cytometry. Confocal microscopy was used to detect DNA damage. The Western blot technique determined the level of nitric oxide synthase and heat shock proteins. Here, for the first time, 2-ME is shown to induce nitro-oxidative stress with the concomitant modulation of heat shock proteins (HSPs) in the SW1088 grade III glioma cell line. Crucial therapeutic strategies for GMB should address both cell proliferation and angiogenesis, and due to the above, 2-ME seems to be a perfect candidate for GBM therapy. MDPI 2022-10-12 /pmc/articles/PMC9598669/ /pubmed/36290736 http://dx.doi.org/10.3390/antiox11102013 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/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 (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Bastian, Paulina Emilia
Daca, Agnieszka
Płoska, Agata
Kuban-Jankowska, Alicja
Kalinowski, Leszek
Gorska-Ponikowska, Magdalena
2-Methoxyestradiol Damages DNA in Glioblastoma Cells by Regulating nNOS and Heat Shock Proteins
title 2-Methoxyestradiol Damages DNA in Glioblastoma Cells by Regulating nNOS and Heat Shock Proteins
title_full 2-Methoxyestradiol Damages DNA in Glioblastoma Cells by Regulating nNOS and Heat Shock Proteins
title_fullStr 2-Methoxyestradiol Damages DNA in Glioblastoma Cells by Regulating nNOS and Heat Shock Proteins
title_full_unstemmed 2-Methoxyestradiol Damages DNA in Glioblastoma Cells by Regulating nNOS and Heat Shock Proteins
title_short 2-Methoxyestradiol Damages DNA in Glioblastoma Cells by Regulating nNOS and Heat Shock Proteins
title_sort 2-methoxyestradiol damages dna in glioblastoma cells by regulating nnos and heat shock proteins
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9598669/
https://www.ncbi.nlm.nih.gov/pubmed/36290736
http://dx.doi.org/10.3390/antiox11102013
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