Cargando…

Flubendazole exhibits anti-glioblastoma effect by inhibiting STAT3 and promoting cell cycle arrest

Glioblastoma multiforme (GBM) belongs to most aggressive and invasive primary brain tumor in adults whose prognosis and survival remains poor. Potential new treatment modalities include targeting the cytoskeleton. In our study, we demonstrated that repurposed drug flubendazole (FLU) significantly in...

Descripción completa

Detalles Bibliográficos
Autores principales: Vítovcová, Barbora, Skarková, Veronika, Havelek, Radim, Soukup, Jiří, Pande, Ananya, Caltová, Kateřina, Rudolf, Emil
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10097688/
https://www.ncbi.nlm.nih.gov/pubmed/37045903
http://dx.doi.org/10.1038/s41598-023-33047-9
_version_ 1785024624787980288
author Vítovcová, Barbora
Skarková, Veronika
Havelek, Radim
Soukup, Jiří
Pande, Ananya
Caltová, Kateřina
Rudolf, Emil
author_facet Vítovcová, Barbora
Skarková, Veronika
Havelek, Radim
Soukup, Jiří
Pande, Ananya
Caltová, Kateřina
Rudolf, Emil
author_sort Vítovcová, Barbora
collection PubMed
description Glioblastoma multiforme (GBM) belongs to most aggressive and invasive primary brain tumor in adults whose prognosis and survival remains poor. Potential new treatment modalities include targeting the cytoskeleton. In our study, we demonstrated that repurposed drug flubendazole (FLU) significantly inhibits proliferation and survival of GBM cells. FLU exerted its effect by affecting microtubule structure and our results also suggest that FLU influences tubulins expression to a certain degree. Moreover, FLU effects decreased activation of STAT3 and also partially inhibited its expression, leading to upregulation of p53 signaling pathway and subsequent cell cycle arrest at G2/M phase as well as caspase-dependent cell death in GBM cells. These results suggest FLU as a promising agent to be used in GBM treatment and prompting further testing of its effects on GBM.
format Online
Article
Text
id pubmed-10097688
institution National Center for Biotechnology Information
language English
publishDate 2023
publisher Nature Publishing Group UK
record_format MEDLINE/PubMed
spelling pubmed-100976882023-04-14 Flubendazole exhibits anti-glioblastoma effect by inhibiting STAT3 and promoting cell cycle arrest Vítovcová, Barbora Skarková, Veronika Havelek, Radim Soukup, Jiří Pande, Ananya Caltová, Kateřina Rudolf, Emil Sci Rep Article Glioblastoma multiforme (GBM) belongs to most aggressive and invasive primary brain tumor in adults whose prognosis and survival remains poor. Potential new treatment modalities include targeting the cytoskeleton. In our study, we demonstrated that repurposed drug flubendazole (FLU) significantly inhibits proliferation and survival of GBM cells. FLU exerted its effect by affecting microtubule structure and our results also suggest that FLU influences tubulins expression to a certain degree. Moreover, FLU effects decreased activation of STAT3 and also partially inhibited its expression, leading to upregulation of p53 signaling pathway and subsequent cell cycle arrest at G2/M phase as well as caspase-dependent cell death in GBM cells. These results suggest FLU as a promising agent to be used in GBM treatment and prompting further testing of its effects on GBM. Nature Publishing Group UK 2023-04-12 /pmc/articles/PMC10097688/ /pubmed/37045903 http://dx.doi.org/10.1038/s41598-023-33047-9 Text en © The Author(s) 2023, corrected publication 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Vítovcová, Barbora
Skarková, Veronika
Havelek, Radim
Soukup, Jiří
Pande, Ananya
Caltová, Kateřina
Rudolf, Emil
Flubendazole exhibits anti-glioblastoma effect by inhibiting STAT3 and promoting cell cycle arrest
title Flubendazole exhibits anti-glioblastoma effect by inhibiting STAT3 and promoting cell cycle arrest
title_full Flubendazole exhibits anti-glioblastoma effect by inhibiting STAT3 and promoting cell cycle arrest
title_fullStr Flubendazole exhibits anti-glioblastoma effect by inhibiting STAT3 and promoting cell cycle arrest
title_full_unstemmed Flubendazole exhibits anti-glioblastoma effect by inhibiting STAT3 and promoting cell cycle arrest
title_short Flubendazole exhibits anti-glioblastoma effect by inhibiting STAT3 and promoting cell cycle arrest
title_sort flubendazole exhibits anti-glioblastoma effect by inhibiting stat3 and promoting cell cycle arrest
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10097688/
https://www.ncbi.nlm.nih.gov/pubmed/37045903
http://dx.doi.org/10.1038/s41598-023-33047-9
work_keys_str_mv AT vitovcovabarbora flubendazoleexhibitsantiglioblastomaeffectbyinhibitingstat3andpromotingcellcyclearrest
AT skarkovaveronika flubendazoleexhibitsantiglioblastomaeffectbyinhibitingstat3andpromotingcellcyclearrest
AT havelekradim flubendazoleexhibitsantiglioblastomaeffectbyinhibitingstat3andpromotingcellcyclearrest
AT soukupjiri flubendazoleexhibitsantiglioblastomaeffectbyinhibitingstat3andpromotingcellcyclearrest
AT pandeananya flubendazoleexhibitsantiglioblastomaeffectbyinhibitingstat3andpromotingcellcyclearrest
AT caltovakaterina flubendazoleexhibitsantiglioblastomaeffectbyinhibitingstat3andpromotingcellcyclearrest
AT rudolfemil flubendazoleexhibitsantiglioblastomaeffectbyinhibitingstat3andpromotingcellcyclearrest