PMA and ionomycin induce glioblastoma cell death: activation-induced cell-death-like phenomena occur in glioma cells.

Phorbol myristate acetate (PMA) and ionomycin (Io) can induce T cell activation and proliferation. Furthermore, they stimulate activation-induced cell death (AICD) in mature lymphocytes via Fas/Fas ligand (FasL) up-regulation. In this study, we explored the influence of PMA/Io treatment on glioblast...

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Main Authors: Sheng Han, Xinxin Tie, Lingxuan Meng, Yunjie Wang, Anhua Wu
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2013-01-01
Series:PLoS ONE
Online Access:http://europepmc.org/articles/PMC3793914?pdf=render
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spelling doaj-ef7886189d4a424493480027b2168ec92020-11-25T02:35:18ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-01810e7671710.1371/journal.pone.0076717PMA and ionomycin induce glioblastoma cell death: activation-induced cell-death-like phenomena occur in glioma cells.Sheng HanXinxin TieLingxuan MengYunjie WangAnhua WuPhorbol myristate acetate (PMA) and ionomycin (Io) can induce T cell activation and proliferation. Furthermore, they stimulate activation-induced cell death (AICD) in mature lymphocytes via Fas/Fas ligand (FasL) up-regulation. In this study, we explored the influence of PMA/Io treatment on glioblastoma cells, and found that AICD-like phenomena may also occur in glioma. Using the MTT assay and cell counting, we demonstrated that treatment of PMA/Io significantly inhibited the proliferation of glioma cell lines, U87 and U251. TUNEL assays and transmission electron microscopy revealed that PMA/Io markedly induced U87 and U251 cell apoptosis. Propidium iodide staining and flow cytometry showed that treatment with PMA/Io resulted in an arrestment of cell cycle and an increase in cell death. Using real-time PCR and western blot, we found that PMA/Io up-regulated the expression of Fas and FasL at both mRNA and protein level, which confirmed that PMA/Io induced glioma cell death. Specific knockdown of NFAT1 expression by small hairpin RNA greatly reduced the PMA/Io induced cell death and apoptosis by inhibition of FasL expression. Microarray analysis showed that the expression of NFAT1 significantly correlated with the expression of Fas. The coexistence of Fas with NFAT1 in vivo provides the background for AICD-like phenomena to occur in glioma. These findings demonstrate that PMA/Io can induce glioblastoma cell death through the NFAT1-Fas/FasL pathway. Glioma-related AICD-like phenomena may provide a novel avenue for glioma treatment.http://europepmc.org/articles/PMC3793914?pdf=render
collection DOAJ
language English
format Article
sources DOAJ
author Sheng Han
Xinxin Tie
Lingxuan Meng
Yunjie Wang
Anhua Wu
spellingShingle Sheng Han
Xinxin Tie
Lingxuan Meng
Yunjie Wang
Anhua Wu
PMA and ionomycin induce glioblastoma cell death: activation-induced cell-death-like phenomena occur in glioma cells.
PLoS ONE
author_facet Sheng Han
Xinxin Tie
Lingxuan Meng
Yunjie Wang
Anhua Wu
author_sort Sheng Han
title PMA and ionomycin induce glioblastoma cell death: activation-induced cell-death-like phenomena occur in glioma cells.
title_short PMA and ionomycin induce glioblastoma cell death: activation-induced cell-death-like phenomena occur in glioma cells.
title_full PMA and ionomycin induce glioblastoma cell death: activation-induced cell-death-like phenomena occur in glioma cells.
title_fullStr PMA and ionomycin induce glioblastoma cell death: activation-induced cell-death-like phenomena occur in glioma cells.
title_full_unstemmed PMA and ionomycin induce glioblastoma cell death: activation-induced cell-death-like phenomena occur in glioma cells.
title_sort pma and ionomycin induce glioblastoma cell death: activation-induced cell-death-like phenomena occur in glioma cells.
publisher Public Library of Science (PLoS)
series PLoS ONE
issn 1932-6203
publishDate 2013-01-01
description Phorbol myristate acetate (PMA) and ionomycin (Io) can induce T cell activation and proliferation. Furthermore, they stimulate activation-induced cell death (AICD) in mature lymphocytes via Fas/Fas ligand (FasL) up-regulation. In this study, we explored the influence of PMA/Io treatment on glioblastoma cells, and found that AICD-like phenomena may also occur in glioma. Using the MTT assay and cell counting, we demonstrated that treatment of PMA/Io significantly inhibited the proliferation of glioma cell lines, U87 and U251. TUNEL assays and transmission electron microscopy revealed that PMA/Io markedly induced U87 and U251 cell apoptosis. Propidium iodide staining and flow cytometry showed that treatment with PMA/Io resulted in an arrestment of cell cycle and an increase in cell death. Using real-time PCR and western blot, we found that PMA/Io up-regulated the expression of Fas and FasL at both mRNA and protein level, which confirmed that PMA/Io induced glioma cell death. Specific knockdown of NFAT1 expression by small hairpin RNA greatly reduced the PMA/Io induced cell death and apoptosis by inhibition of FasL expression. Microarray analysis showed that the expression of NFAT1 significantly correlated with the expression of Fas. The coexistence of Fas with NFAT1 in vivo provides the background for AICD-like phenomena to occur in glioma. These findings demonstrate that PMA/Io can induce glioblastoma cell death through the NFAT1-Fas/FasL pathway. Glioma-related AICD-like phenomena may provide a novel avenue for glioma treatment.
url http://europepmc.org/articles/PMC3793914?pdf=render
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