Panobinostat and its combination with 3-deazaneplanocin-A induce apoptosis and inhibit In vitro tumorigenesis and metastasis in GOS-3 glioblastoma cell lines
Aim: Glioblastoma is the most malignant primary brain tumor. The treatment consists of surgery, with or without radiotherapy, and temozolomide, with a life expectancy of 12–15 months after diagnosis. Glioblastoma is resistant to conventional antitumor therapies. In this work, we present a preliminar...
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doaj-110953a4c33a4fc19f69228507d8bf572020-11-24T21:48:04ZengWolters Kluwer Medknow PublicationsCancer Translational Medicine2395-39772395-30122018-01-0142394710.4103/ctm.ctm_12_18Panobinostat and its combination with 3-deazaneplanocin-A induce apoptosis and inhibit In vitro tumorigenesis and metastasis in GOS-3 glioblastoma cell linesJavier de la RosaAlejandro UrdiciainJuan Jesús Aznar-MoralesBárbara MeléndezJuan A ReyMiguel A IdoateJavier S CastresanaAim: Glioblastoma is the most malignant primary brain tumor. The treatment consists of surgery, with or without radiotherapy, and temozolomide, with a life expectancy of 12–15 months after diagnosis. Glioblastoma is resistant to conventional antitumor therapies. In this work, we present a preliminary in vitro study of two epigenetic drugs against GOS-3 glioblastoma cells. Methods: We used (1) panobinostat, a histone deacetylase inhibitor, and (2) 3-deazaneplanocin-A (DZ-Nep), an inhibitor of enhancer of zeste homolog 2 (EZH2) (enzyme of the polycomb repressor complex 2, polycomb group of proteins that trimethylate lysine 27 of histone 3-H3K27 me3-), as treatments that might modulate the PI3K pathway, affected in GOS-3 cells due to PTEN haploinsufficiency. The glioblastoma cell line GOS-3 was exposed to DZ-Nep and panobinostat treatments, separately and in combination, over a period of 2 days, after which cell migration, clonogenicity, and molecular expression characterization assays were performed. Results: Panobinostat alone or the combination of panobinostat plus DZ-Nep inhibited clonogenicity, metastasis, angiogenesis, epithelial–mesenchymal transition, and entry in the S phase of the cell cycle and induced apoptosis in GOS-3 glioblastoma cells. On the contrary, DZ-Nep inhibited cell migration (single treatment) and O(6)-methylguanine-DNA methyltransferase expression (DZ-Nep or double treatment). Conclusion: Panobinostat alone or the combination of panobinostat and DZ-Nep induce apoptosis and inhibit in vitro tumorigenesis and metastasis in GOS-3 glioblastoma cell lines.http://www.cancertm.com/article.asp?issn=2395-3977;year=2018;volume=4;issue=2;spage=39;epage=47;aulast=de3-Deazaneplanocin-Aenhancer of zeste homolog 2epigeneticshistone deacetylasespanobinostat |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Javier de la Rosa Alejandro Urdiciain Juan Jesús Aznar-Morales Bárbara Meléndez Juan A Rey Miguel A Idoate Javier S Castresana |
spellingShingle |
Javier de la Rosa Alejandro Urdiciain Juan Jesús Aznar-Morales Bárbara Meléndez Juan A Rey Miguel A Idoate Javier S Castresana Panobinostat and its combination with 3-deazaneplanocin-A induce apoptosis and inhibit In vitro tumorigenesis and metastasis in GOS-3 glioblastoma cell lines Cancer Translational Medicine 3-Deazaneplanocin-A enhancer of zeste homolog 2 epigenetics histone deacetylases panobinostat |
author_facet |
Javier de la Rosa Alejandro Urdiciain Juan Jesús Aznar-Morales Bárbara Meléndez Juan A Rey Miguel A Idoate Javier S Castresana |
author_sort |
Javier de la Rosa |
title |
Panobinostat and its combination with 3-deazaneplanocin-A induce apoptosis and inhibit In vitro tumorigenesis and metastasis in GOS-3 glioblastoma cell lines |
title_short |
Panobinostat and its combination with 3-deazaneplanocin-A induce apoptosis and inhibit In vitro tumorigenesis and metastasis in GOS-3 glioblastoma cell lines |
title_full |
Panobinostat and its combination with 3-deazaneplanocin-A induce apoptosis and inhibit In vitro tumorigenesis and metastasis in GOS-3 glioblastoma cell lines |
title_fullStr |
Panobinostat and its combination with 3-deazaneplanocin-A induce apoptosis and inhibit In vitro tumorigenesis and metastasis in GOS-3 glioblastoma cell lines |
title_full_unstemmed |
Panobinostat and its combination with 3-deazaneplanocin-A induce apoptosis and inhibit In vitro tumorigenesis and metastasis in GOS-3 glioblastoma cell lines |
title_sort |
panobinostat and its combination with 3-deazaneplanocin-a induce apoptosis and inhibit in vitro tumorigenesis and metastasis in gos-3 glioblastoma cell lines |
publisher |
Wolters Kluwer Medknow Publications |
series |
Cancer Translational Medicine |
issn |
2395-3977 2395-3012 |
publishDate |
2018-01-01 |
description |
Aim: Glioblastoma is the most malignant primary brain tumor. The treatment consists of surgery, with or without radiotherapy, and temozolomide, with a life expectancy of 12–15 months after diagnosis. Glioblastoma is resistant to conventional antitumor therapies. In this work, we present a preliminary in vitro study of two epigenetic drugs against GOS-3 glioblastoma cells.
Methods: We used (1) panobinostat, a histone deacetylase inhibitor, and (2) 3-deazaneplanocin-A (DZ-Nep), an inhibitor of enhancer of zeste homolog 2 (EZH2) (enzyme of the polycomb repressor complex 2, polycomb group of proteins that trimethylate lysine 27 of histone 3-H3K27 me3-), as treatments that might modulate the PI3K pathway, affected in GOS-3 cells due to PTEN haploinsufficiency. The glioblastoma cell line GOS-3 was exposed to DZ-Nep and panobinostat treatments, separately and in combination, over a period of 2 days, after which cell migration, clonogenicity, and molecular expression characterization assays were performed.
Results: Panobinostat alone or the combination of panobinostat plus DZ-Nep inhibited clonogenicity, metastasis, angiogenesis, epithelial–mesenchymal transition, and entry in the S phase of the cell cycle and induced apoptosis in GOS-3 glioblastoma cells. On the contrary, DZ-Nep inhibited cell migration (single treatment) and O(6)-methylguanine-DNA methyltransferase expression (DZ-Nep or double treatment).
Conclusion: Panobinostat alone or the combination of panobinostat and DZ-Nep induce apoptosis and inhibit in vitro tumorigenesis and metastasis in GOS-3 glioblastoma cell lines. |
topic |
3-Deazaneplanocin-A enhancer of zeste homolog 2 epigenetics histone deacetylases panobinostat |
url |
http://www.cancertm.com/article.asp?issn=2395-3977;year=2018;volume=4;issue=2;spage=39;epage=47;aulast=de |
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