Cargando…

Role for Metallothionein-3 in the Resistance of Human U87 Glioblastoma Cells to Temozolomide

[Image: see text] Metallothioneins (MTs) are metal-binding proteins that are overexpressed in various human cancers and are thought to be associated with resistance to cytotoxic drugs. The knowledge on MT expression, regulation, and function in human gliomas is limited. We found that MT3 mRNA was hi...

Descripción completa

Detalles Bibliográficos
Autores principales: Santangelo, Rosa, Rizzarelli, Enrico, Copani, Agata
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Chemical Society 2020
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7392386/
https://www.ncbi.nlm.nih.gov/pubmed/32743161
http://dx.doi.org/10.1021/acsomega.9b04483
_version_ 1783564837791465472
author Santangelo, Rosa
Rizzarelli, Enrico
Copani, Agata
author_facet Santangelo, Rosa
Rizzarelli, Enrico
Copani, Agata
author_sort Santangelo, Rosa
collection PubMed
description [Image: see text] Metallothioneins (MTs) are metal-binding proteins that are overexpressed in various human cancers and are thought to be associated with resistance to cytotoxic drugs. The knowledge on MT expression, regulation, and function in human gliomas is limited. We found that MT3 mRNA was highly expressed in cell lines derived from grade IV gliomas (i.e., A172 and U87 cells), as compared to grade II astrocytoma cells (i.e., 1321N1). Different from 1321N1, U87 cells were partly resistant to the alkylating drug, temozolomide (TMZ) (100 μM for 96 h), which induced a massive accumulation of U87 into the S and G2 fractions of the cell cycle but not apoptotic death. Silencing of MT3 did not significantly affect U87 cell proliferation and survival, but it delayed G1/S transition and favored the occurrence of apoptosis in TMZ-treated cells. Accordingly, the combination of MT3 silencing and TMZ treatment increased the protein levels of checkpoint kinase-1, which was ultimately responsible for the lasting G1 arrest and death of double treated U87 cells.
format Online
Article
Text
id pubmed-7392386
institution National Center for Biotechnology Information
language English
publishDate 2020
publisher American Chemical Society
record_format MEDLINE/PubMed
spelling pubmed-73923862020-07-31 Role for Metallothionein-3 in the Resistance of Human U87 Glioblastoma Cells to Temozolomide Santangelo, Rosa Rizzarelli, Enrico Copani, Agata ACS Omega [Image: see text] Metallothioneins (MTs) are metal-binding proteins that are overexpressed in various human cancers and are thought to be associated with resistance to cytotoxic drugs. The knowledge on MT expression, regulation, and function in human gliomas is limited. We found that MT3 mRNA was highly expressed in cell lines derived from grade IV gliomas (i.e., A172 and U87 cells), as compared to grade II astrocytoma cells (i.e., 1321N1). Different from 1321N1, U87 cells were partly resistant to the alkylating drug, temozolomide (TMZ) (100 μM for 96 h), which induced a massive accumulation of U87 into the S and G2 fractions of the cell cycle but not apoptotic death. Silencing of MT3 did not significantly affect U87 cell proliferation and survival, but it delayed G1/S transition and favored the occurrence of apoptosis in TMZ-treated cells. Accordingly, the combination of MT3 silencing and TMZ treatment increased the protein levels of checkpoint kinase-1, which was ultimately responsible for the lasting G1 arrest and death of double treated U87 cells. American Chemical Society 2020-07-16 /pmc/articles/PMC7392386/ /pubmed/32743161 http://dx.doi.org/10.1021/acsomega.9b04483 Text en Copyright © 2020 American Chemical Society This is an open access article published under an ACS AuthorChoice License (http://pubs.acs.org/page/policy/authorchoice_termsofuse.html) , which permits copying and redistribution of the article or any adaptations for non-commercial purposes.
spellingShingle Santangelo, Rosa
Rizzarelli, Enrico
Copani, Agata
Role for Metallothionein-3 in the Resistance of Human U87 Glioblastoma Cells to Temozolomide
title Role for Metallothionein-3 in the Resistance of Human U87 Glioblastoma Cells to Temozolomide
title_full Role for Metallothionein-3 in the Resistance of Human U87 Glioblastoma Cells to Temozolomide
title_fullStr Role for Metallothionein-3 in the Resistance of Human U87 Glioblastoma Cells to Temozolomide
title_full_unstemmed Role for Metallothionein-3 in the Resistance of Human U87 Glioblastoma Cells to Temozolomide
title_short Role for Metallothionein-3 in the Resistance of Human U87 Glioblastoma Cells to Temozolomide
title_sort role for metallothionein-3 in the resistance of human u87 glioblastoma cells to temozolomide
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7392386/
https://www.ncbi.nlm.nih.gov/pubmed/32743161
http://dx.doi.org/10.1021/acsomega.9b04483
work_keys_str_mv AT santangelorosa roleformetallothionein3intheresistanceofhumanu87glioblastomacellstotemozolomide
AT rizzarellienrico roleformetallothionein3intheresistanceofhumanu87glioblastomacellstotemozolomide
AT copaniagata roleformetallothionein3intheresistanceofhumanu87glioblastomacellstotemozolomide