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Propranolol Inhibits the Proliferation of Human Glioblastoma Cell Lines through Notch1 and Hes1 Signaling System

OBJECTIVE: The anti-tumor effect of the beta-adrenergic receptor antagonist propranolol in breast cancer is well known; however, its activity in glioblastoma is not well-evaluated. The Notch-Hes pathway is known to regulate cell differentiation, proliferation, and apoptosis. We investigated the effe...

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Autores principales: Kim, Hyun Sik, Park, Young Han, Lee, Heui Seung, Kwon, Mi Jung, Song, Joon Ho, Chang, In Bok
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Korean Neurosurgical Society 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8435645/
https://www.ncbi.nlm.nih.gov/pubmed/34376038
http://dx.doi.org/10.3340/jkns.2021.0068
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author Kim, Hyun Sik
Park, Young Han
Lee, Heui Seung
Kwon, Mi Jung
Song, Joon Ho
Chang, In Bok
author_facet Kim, Hyun Sik
Park, Young Han
Lee, Heui Seung
Kwon, Mi Jung
Song, Joon Ho
Chang, In Bok
author_sort Kim, Hyun Sik
collection PubMed
description OBJECTIVE: The anti-tumor effect of the beta-adrenergic receptor antagonist propranolol in breast cancer is well known; however, its activity in glioblastoma is not well-evaluated. The Notch-Hes pathway is known to regulate cell differentiation, proliferation, and apoptosis. We investigated the effect of propranolol to human glioblastoma cell lines, and the role of Notch and Hes signaling in this process. METHODS: We performed immunohistochemical staining on 31 surgically resected primary human glioblastoma tissues. We also used glioblastoma cell lines of U87-MG, LN229, and neuroblastoma cell line of SH-SY5Y in this study. The effect of propranolol and isoproterenol on cell proliferation was evaluated using the MTT assay (absorbance 570 nm). The impact of propranolol on gene expression (Notch and Hes) was evaluated using real-time polymerase chain reaction (RT-PCR, whereas protein levels of Notch1 and Hes1 were measured using Western blotting (WB), simultaneously. Small interfering RNA (siRNA) was used to suppress the Notch gene to investigate its role in the proliferation of glioblastoma. RESULTS: Propranolol and isoproterenol caused a dose-dependent decrease in cell proliferation (MTT assay). RT-PCR showed an increase in Notch1 and Hes1 expression by propranolol, whereas WB demonstrated increase in Notch1 protein, but a decrease in Hes1 by propranolol. The proliferation of U87-MG and LN229 was not significantly suppressed after transfection with Notch siRNA. CONCLUSION: These results demonstrated that propranolol suppressed the proliferation of glioblastoma cell lines and neuroblastoma cell line, and Hes1 was more closely involved than Notch1 was in glioblastoma proliferation.
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spelling pubmed-84356452021-09-20 Propranolol Inhibits the Proliferation of Human Glioblastoma Cell Lines through Notch1 and Hes1 Signaling System Kim, Hyun Sik Park, Young Han Lee, Heui Seung Kwon, Mi Jung Song, Joon Ho Chang, In Bok J Korean Neurosurg Soc Laboratory Investigation OBJECTIVE: The anti-tumor effect of the beta-adrenergic receptor antagonist propranolol in breast cancer is well known; however, its activity in glioblastoma is not well-evaluated. The Notch-Hes pathway is known to regulate cell differentiation, proliferation, and apoptosis. We investigated the effect of propranolol to human glioblastoma cell lines, and the role of Notch and Hes signaling in this process. METHODS: We performed immunohistochemical staining on 31 surgically resected primary human glioblastoma tissues. We also used glioblastoma cell lines of U87-MG, LN229, and neuroblastoma cell line of SH-SY5Y in this study. The effect of propranolol and isoproterenol on cell proliferation was evaluated using the MTT assay (absorbance 570 nm). The impact of propranolol on gene expression (Notch and Hes) was evaluated using real-time polymerase chain reaction (RT-PCR, whereas protein levels of Notch1 and Hes1 were measured using Western blotting (WB), simultaneously. Small interfering RNA (siRNA) was used to suppress the Notch gene to investigate its role in the proliferation of glioblastoma. RESULTS: Propranolol and isoproterenol caused a dose-dependent decrease in cell proliferation (MTT assay). RT-PCR showed an increase in Notch1 and Hes1 expression by propranolol, whereas WB demonstrated increase in Notch1 protein, but a decrease in Hes1 by propranolol. The proliferation of U87-MG and LN229 was not significantly suppressed after transfection with Notch siRNA. CONCLUSION: These results demonstrated that propranolol suppressed the proliferation of glioblastoma cell lines and neuroblastoma cell line, and Hes1 was more closely involved than Notch1 was in glioblastoma proliferation. Korean Neurosurgical Society 2021-09 2021-08-11 /pmc/articles/PMC8435645/ /pubmed/34376038 http://dx.doi.org/10.3340/jkns.2021.0068 Text en Copyright © 2021 The Korean Neurosurgical Society https://creativecommons.org/licenses/by-nc/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0 (https://creativecommons.org/licenses/by-nc/4.0/) ) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Laboratory Investigation
Kim, Hyun Sik
Park, Young Han
Lee, Heui Seung
Kwon, Mi Jung
Song, Joon Ho
Chang, In Bok
Propranolol Inhibits the Proliferation of Human Glioblastoma Cell Lines through Notch1 and Hes1 Signaling System
title Propranolol Inhibits the Proliferation of Human Glioblastoma Cell Lines through Notch1 and Hes1 Signaling System
title_full Propranolol Inhibits the Proliferation of Human Glioblastoma Cell Lines through Notch1 and Hes1 Signaling System
title_fullStr Propranolol Inhibits the Proliferation of Human Glioblastoma Cell Lines through Notch1 and Hes1 Signaling System
title_full_unstemmed Propranolol Inhibits the Proliferation of Human Glioblastoma Cell Lines through Notch1 and Hes1 Signaling System
title_short Propranolol Inhibits the Proliferation of Human Glioblastoma Cell Lines through Notch1 and Hes1 Signaling System
title_sort propranolol inhibits the proliferation of human glioblastoma cell lines through notch1 and hes1 signaling system
topic Laboratory Investigation
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8435645/
https://www.ncbi.nlm.nih.gov/pubmed/34376038
http://dx.doi.org/10.3340/jkns.2021.0068
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