In vitro therapy against glioblastoma cells by 3-Dezaneplanocin-A, panobinostat, and temozolomide
Background: Glioblastoma multiforme (GBM) is the most malignant primary brain tumor. Current treatment against this tumor consists of maximal surgical resection without threatening the patient's life, followed by a treatment with temozolomide, with or without combined radiotherapy. GBM is resis...
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doaj-5c03536fc96e4c8687904ebb087a99a42020-11-25T00:02:14ZengWolters Kluwer Medknow PublicationsGlioma2589-61132589-61212018-01-0111222610.4103/glioma.glioma_6_18In vitro therapy against glioblastoma cells by 3-Dezaneplanocin-A, panobinostat, and temozolomideJavier de la RosaAlejandro UrdiciainBárbara MeléndezJuan A ReyMiguel A IdoateJavier S CastresanaBackground: Glioblastoma multiforme (GBM) is the most malignant primary brain tumor. Current treatment against this tumor consists of maximal surgical resection without threatening the patient's life, followed by a treatment with temozolomide, with or without combined radiotherapy. GBM is resistant to the conventional antitumor therapies, so in this research, we tried to inhibit tumor growth with the combination of three drugs: (1) panobinostat, an inhibitor of histone deacetylases, (2) 3-Dezaneplanocin-A (DZNep), an inhibitor of EZH2, a protein which belongs to the polycomb repressor complex 2, acting as a histone methylase, and (3) temozolomide, an alkylating agent. Methods: The T98G GBM commercial cell line was used. Cells were exposed to single treatments of the drugs and to the three possible combinations among them. Soon after, two-dimensional (2D) and 3D clonogenic assays were assessed for in vitro tumorigenicity testing. Real-time quantitative polymerase chain reaction of 2 proapoptotic genes (BAX and NOXA) and 2 antiapoptotic genes (BCL2 and BCL-XL) was also assessed. Results: The panobinostat and temozolomide combination produced a positive effect against T98G glioblastoma cells by reducing soft agar colony formation, by inducing high expression levels of NOXA, and by reducing BCL-XL expression. Equally, the panobinostat and DZNep combination produced a positive effect against T98G glioblastoma cells by reducing colony formation in adherent conditions and by inducing high expression levels of BAX. Finally, temozolomide alone was the most efficient drug for decreasing BCL2 expression. Conclusion: Panobinostat and temozolomide combination or panobinostat and DZNep combination might be more efficient against glioblastoma cells than just temozolomide.http://www.jglioma.com/article.asp?issn=2589-6113;year=2018;volume=1;issue=1;spage=22;epage=26;aulast=deBrain tumorsepigeneticsEZH2histone deacetylasehistone methylase |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Javier de la Rosa Alejandro Urdiciain Bárbara Meléndez Juan A Rey Miguel A Idoate Javier S Castresana |
spellingShingle |
Javier de la Rosa Alejandro Urdiciain Bárbara Meléndez Juan A Rey Miguel A Idoate Javier S Castresana In vitro therapy against glioblastoma cells by 3-Dezaneplanocin-A, panobinostat, and temozolomide Glioma Brain tumors epigenetics EZH2 histone deacetylase histone methylase |
author_facet |
Javier de la Rosa Alejandro Urdiciain Bárbara Meléndez Juan A Rey Miguel A Idoate Javier S Castresana |
author_sort |
Javier de la Rosa |
title |
In vitro therapy against glioblastoma cells by 3-Dezaneplanocin-A, panobinostat, and temozolomide |
title_short |
In vitro therapy against glioblastoma cells by 3-Dezaneplanocin-A, panobinostat, and temozolomide |
title_full |
In vitro therapy against glioblastoma cells by 3-Dezaneplanocin-A, panobinostat, and temozolomide |
title_fullStr |
In vitro therapy against glioblastoma cells by 3-Dezaneplanocin-A, panobinostat, and temozolomide |
title_full_unstemmed |
In vitro therapy against glioblastoma cells by 3-Dezaneplanocin-A, panobinostat, and temozolomide |
title_sort |
in vitro therapy against glioblastoma cells by 3-dezaneplanocin-a, panobinostat, and temozolomide |
publisher |
Wolters Kluwer Medknow Publications |
series |
Glioma |
issn |
2589-6113 2589-6121 |
publishDate |
2018-01-01 |
description |
Background: Glioblastoma multiforme (GBM) is the most malignant primary brain tumor. Current treatment against this tumor consists of maximal surgical resection without threatening the patient's life, followed by a treatment with temozolomide, with or without combined radiotherapy. GBM is resistant to the conventional antitumor therapies, so in this research, we tried to inhibit tumor growth with the combination of three drugs: (1) panobinostat, an inhibitor of histone deacetylases, (2) 3-Dezaneplanocin-A (DZNep), an inhibitor of EZH2, a protein which belongs to the polycomb repressor complex 2, acting as a histone methylase, and (3) temozolomide, an alkylating agent. Methods: The T98G GBM commercial cell line was used. Cells were exposed to single treatments of the drugs and to the three possible combinations among them. Soon after, two-dimensional (2D) and 3D clonogenic assays were assessed for in vitro tumorigenicity testing. Real-time quantitative polymerase chain reaction of 2 proapoptotic genes (BAX and NOXA) and 2 antiapoptotic genes (BCL2 and BCL-XL) was also assessed. Results: The panobinostat and temozolomide combination produced a positive effect against T98G glioblastoma cells by reducing soft agar colony formation, by inducing high expression levels of NOXA, and by reducing BCL-XL expression. Equally, the panobinostat and DZNep combination produced a positive effect against T98G glioblastoma cells by reducing colony formation in adherent conditions and by inducing high expression levels of BAX. Finally, temozolomide alone was the most efficient drug for decreasing BCL2 expression. Conclusion: Panobinostat and temozolomide combination or panobinostat and DZNep combination might be more efficient against glioblastoma cells than just temozolomide. |
topic |
Brain tumors epigenetics EZH2 histone deacetylase histone methylase |
url |
http://www.jglioma.com/article.asp?issn=2589-6113;year=2018;volume=1;issue=1;spage=22;epage=26;aulast=de |
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