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Antioxidant and Antiproliferative Activity of Finasteride against Glioblastoma Cells

Glioblastoma is an actively growing and aggressive brain tumor with a high propensity of recurrence. Although the surgical removal of tumor mass is the primary therapeutic option against glioblastoma, supportive pharmacotherapy is highly essential due to incredibly infiltrative characteristic of gli...

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Autores principales: Kim, Hyeon Ji, Kim, Tae-Jun, Kim, Yu Gyung, Seong, Chaeeun, Cho, Jin-Hwa, Kim, Wanil, Lee, Kyung-Ha, Kim, Do-Yeon
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8469955/
https://www.ncbi.nlm.nih.gov/pubmed/34575486
http://dx.doi.org/10.3390/pharmaceutics13091410
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author Kim, Hyeon Ji
Kim, Tae-Jun
Kim, Yu Gyung
Seong, Chaeeun
Cho, Jin-Hwa
Kim, Wanil
Lee, Kyung-Ha
Kim, Do-Yeon
author_facet Kim, Hyeon Ji
Kim, Tae-Jun
Kim, Yu Gyung
Seong, Chaeeun
Cho, Jin-Hwa
Kim, Wanil
Lee, Kyung-Ha
Kim, Do-Yeon
author_sort Kim, Hyeon Ji
collection PubMed
description Glioblastoma is an actively growing and aggressive brain tumor with a high propensity of recurrence. Although the surgical removal of tumor mass is the primary therapeutic option against glioblastoma, supportive pharmacotherapy is highly essential due to incredibly infiltrative characteristic of glioblastoma. Temozolomide, an FDA-approved alkylating agent, has been used as a first-line standard pharmacological approach, but several evident limitations were repeatedly reported. Despite additional therapeutic options suggested, there are no medications that successfully prevent a recurrence of glioblastoma and increase the five-year survival rate. In this study, we tested the possibility that finasteride has the potential to be developed as an anti-glioblastoma drug. Finasteride, an FDA-approved medication for the treatment of benign prostate hyperplasia and androgenic alopecia, is already known to pass through the blood–brain barrier and possess antiproliferative activity of prostate epithelial cells. We showed that finasteride inhibited the maintenance of glioma stem-like cells and repressed the proliferation of glioblastoma. Mechanistically, finasteride lowered intracellular ROS level by upregulating antioxidant genes, which contributed to inefficient β-catenin accumulation. Downregulated β-catenin resulted in the reduction in stemness and cell growth in glioblastoma.
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spelling pubmed-84699552021-09-27 Antioxidant and Antiproliferative Activity of Finasteride against Glioblastoma Cells Kim, Hyeon Ji Kim, Tae-Jun Kim, Yu Gyung Seong, Chaeeun Cho, Jin-Hwa Kim, Wanil Lee, Kyung-Ha Kim, Do-Yeon Pharmaceutics Article Glioblastoma is an actively growing and aggressive brain tumor with a high propensity of recurrence. Although the surgical removal of tumor mass is the primary therapeutic option against glioblastoma, supportive pharmacotherapy is highly essential due to incredibly infiltrative characteristic of glioblastoma. Temozolomide, an FDA-approved alkylating agent, has been used as a first-line standard pharmacological approach, but several evident limitations were repeatedly reported. Despite additional therapeutic options suggested, there are no medications that successfully prevent a recurrence of glioblastoma and increase the five-year survival rate. In this study, we tested the possibility that finasteride has the potential to be developed as an anti-glioblastoma drug. Finasteride, an FDA-approved medication for the treatment of benign prostate hyperplasia and androgenic alopecia, is already known to pass through the blood–brain barrier and possess antiproliferative activity of prostate epithelial cells. We showed that finasteride inhibited the maintenance of glioma stem-like cells and repressed the proliferation of glioblastoma. Mechanistically, finasteride lowered intracellular ROS level by upregulating antioxidant genes, which contributed to inefficient β-catenin accumulation. Downregulated β-catenin resulted in the reduction in stemness and cell growth in glioblastoma. MDPI 2021-09-06 /pmc/articles/PMC8469955/ /pubmed/34575486 http://dx.doi.org/10.3390/pharmaceutics13091410 Text en © 2021 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
Kim, Hyeon Ji
Kim, Tae-Jun
Kim, Yu Gyung
Seong, Chaeeun
Cho, Jin-Hwa
Kim, Wanil
Lee, Kyung-Ha
Kim, Do-Yeon
Antioxidant and Antiproliferative Activity of Finasteride against Glioblastoma Cells
title Antioxidant and Antiproliferative Activity of Finasteride against Glioblastoma Cells
title_full Antioxidant and Antiproliferative Activity of Finasteride against Glioblastoma Cells
title_fullStr Antioxidant and Antiproliferative Activity of Finasteride against Glioblastoma Cells
title_full_unstemmed Antioxidant and Antiproliferative Activity of Finasteride against Glioblastoma Cells
title_short Antioxidant and Antiproliferative Activity of Finasteride against Glioblastoma Cells
title_sort antioxidant and antiproliferative activity of finasteride against glioblastoma cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8469955/
https://www.ncbi.nlm.nih.gov/pubmed/34575486
http://dx.doi.org/10.3390/pharmaceutics13091410
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