Cargando…

Lactate dehydrogenase-A inhibition induces human glioblastoma multiforme stem cell differentiation and death

Therapies that target the signal transduction and metabolic pathways of cancer stem cells (CSCs) are innovative strategies to effectively reduce the recurrence and significantly improve the outcome of glioblastoma multiforme (GBM). CSCs exhibit an increased rate of glycolysis, thus rendering them in...

Descripción completa

Detalles Bibliográficos
Autores principales: Daniele, Simona, Giacomelli, Chiara, Zappelli, Elisa, Granchi, Carlotta, Trincavelli, Maria Letizia, Minutolo, Filippo, Martini, Claudia
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4616042/
https://www.ncbi.nlm.nih.gov/pubmed/26494310
http://dx.doi.org/10.1038/srep15556
_version_ 1782396553932046336
author Daniele, Simona
Giacomelli, Chiara
Zappelli, Elisa
Granchi, Carlotta
Trincavelli, Maria Letizia
Minutolo, Filippo
Martini, Claudia
author_facet Daniele, Simona
Giacomelli, Chiara
Zappelli, Elisa
Granchi, Carlotta
Trincavelli, Maria Letizia
Minutolo, Filippo
Martini, Claudia
author_sort Daniele, Simona
collection PubMed
description Therapies that target the signal transduction and metabolic pathways of cancer stem cells (CSCs) are innovative strategies to effectively reduce the recurrence and significantly improve the outcome of glioblastoma multiforme (GBM). CSCs exhibit an increased rate of glycolysis, thus rendering them intrinsically more sensitive to prospective therapeutic strategies based on the inhibition of the glycolytic pathway. The enzyme lactate dehydrogenase-A (LDH-A), which catalyses the interconversion of pyruvate and lactate, is up-regulated in human cancers, including GBM. Although several papers have explored the benefits of targeting cancer metabolism in GBM, the effects of direct LDH-A inhibition in glial tumours have not yet been investigated, particularly in the stem cell subpopulation. Here, two representative LDH-A inhibitors (NHI-1 and NHI-2) were studied in GBM-derived CSCs and compared to differentiated tumour cells. LDH-A inhibition was particularly effective in CSCs isolated from different GBM cell lines, where the two compounds blocked CSC formation and elicited long-lasting effects by triggering both apoptosis and cellular differentiation. These data demonstrate that GBM, particularly the stem cell subpopulation, is sensitive to glycolytic inhibition and shed light on the therapeutic potential of LDH-A inhibitors in this tumour type.
format Online
Article
Text
id pubmed-4616042
institution National Center for Biotechnology Information
language English
publishDate 2015
publisher Nature Publishing Group
record_format MEDLINE/PubMed
spelling pubmed-46160422015-10-29 Lactate dehydrogenase-A inhibition induces human glioblastoma multiforme stem cell differentiation and death Daniele, Simona Giacomelli, Chiara Zappelli, Elisa Granchi, Carlotta Trincavelli, Maria Letizia Minutolo, Filippo Martini, Claudia Sci Rep Article Therapies that target the signal transduction and metabolic pathways of cancer stem cells (CSCs) are innovative strategies to effectively reduce the recurrence and significantly improve the outcome of glioblastoma multiforme (GBM). CSCs exhibit an increased rate of glycolysis, thus rendering them intrinsically more sensitive to prospective therapeutic strategies based on the inhibition of the glycolytic pathway. The enzyme lactate dehydrogenase-A (LDH-A), which catalyses the interconversion of pyruvate and lactate, is up-regulated in human cancers, including GBM. Although several papers have explored the benefits of targeting cancer metabolism in GBM, the effects of direct LDH-A inhibition in glial tumours have not yet been investigated, particularly in the stem cell subpopulation. Here, two representative LDH-A inhibitors (NHI-1 and NHI-2) were studied in GBM-derived CSCs and compared to differentiated tumour cells. LDH-A inhibition was particularly effective in CSCs isolated from different GBM cell lines, where the two compounds blocked CSC formation and elicited long-lasting effects by triggering both apoptosis and cellular differentiation. These data demonstrate that GBM, particularly the stem cell subpopulation, is sensitive to glycolytic inhibition and shed light on the therapeutic potential of LDH-A inhibitors in this tumour type. Nature Publishing Group 2015-10-23 /pmc/articles/PMC4616042/ /pubmed/26494310 http://dx.doi.org/10.1038/srep15556 Text en Copyright © 2015, Macmillan Publishers Limited http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Article
Daniele, Simona
Giacomelli, Chiara
Zappelli, Elisa
Granchi, Carlotta
Trincavelli, Maria Letizia
Minutolo, Filippo
Martini, Claudia
Lactate dehydrogenase-A inhibition induces human glioblastoma multiforme stem cell differentiation and death
title Lactate dehydrogenase-A inhibition induces human glioblastoma multiforme stem cell differentiation and death
title_full Lactate dehydrogenase-A inhibition induces human glioblastoma multiforme stem cell differentiation and death
title_fullStr Lactate dehydrogenase-A inhibition induces human glioblastoma multiforme stem cell differentiation and death
title_full_unstemmed Lactate dehydrogenase-A inhibition induces human glioblastoma multiforme stem cell differentiation and death
title_short Lactate dehydrogenase-A inhibition induces human glioblastoma multiforme stem cell differentiation and death
title_sort lactate dehydrogenase-a inhibition induces human glioblastoma multiforme stem cell differentiation and death
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4616042/
https://www.ncbi.nlm.nih.gov/pubmed/26494310
http://dx.doi.org/10.1038/srep15556
work_keys_str_mv AT danielesimona lactatedehydrogenaseainhibitioninduceshumanglioblastomamultiformestemcelldifferentiationanddeath
AT giacomellichiara lactatedehydrogenaseainhibitioninduceshumanglioblastomamultiformestemcelldifferentiationanddeath
AT zappellielisa lactatedehydrogenaseainhibitioninduceshumanglioblastomamultiformestemcelldifferentiationanddeath
AT granchicarlotta lactatedehydrogenaseainhibitioninduceshumanglioblastomamultiformestemcelldifferentiationanddeath
AT trincavellimarialetizia lactatedehydrogenaseainhibitioninduceshumanglioblastomamultiformestemcelldifferentiationanddeath
AT minutolofilippo lactatedehydrogenaseainhibitioninduceshumanglioblastomamultiformestemcelldifferentiationanddeath
AT martiniclaudia lactatedehydrogenaseainhibitioninduceshumanglioblastomamultiformestemcelldifferentiationanddeath