Cargando…
Activation of Casein Kinase II by Gallic Acid Induces BIK–BAX/BAK-Mediated ER Ca(++)-ROS-Dependent Apoptosis of Human Oral Cancer Cells
Induction of the generation of endoplasmic reticulum (ER) calcium (Ca(++))-mediated reactive oxygen species (ROS) by gallic acid (GA) has been implicated in the mitochondrial apoptotic death of human oral cancer (OC) cells, but the molecular mechanism by which GA causes ER Ca(++) release of OC cells...
Autores principales: | , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2017
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5627504/ https://www.ncbi.nlm.nih.gov/pubmed/29033852 http://dx.doi.org/10.3389/fphys.2017.00761 |
_version_ | 1783268731363786752 |
---|---|
author | Lin, Meng-Liang Chen, Shih-Shun |
author_facet | Lin, Meng-Liang Chen, Shih-Shun |
author_sort | Lin, Meng-Liang |
collection | PubMed |
description | Induction of the generation of endoplasmic reticulum (ER) calcium (Ca(++))-mediated reactive oxygen species (ROS) by gallic acid (GA) has been implicated in the mitochondrial apoptotic death of human oral cancer (OC) cells, but the molecular mechanism by which GA causes ER Ca(++) release of OC cells to undergo cell death remains unclear. Here, we report that GA-induced phosphorylation of B-cell lymphoma 2 (BCL-2)-interacting killer (BIK) (threonine (Thr) 33/Serine (Ser) 35) and p53 (Ser 15 and Ser 392), Bcl-2-associated x protein (BAX)/BCL-2 antagonist killer 1 (BAK) oligomerization on the ER and mitochondria, rising of cytosolic Ca(+)(+) and ROS, cytochrome c (Cyt c) release from the mitochondria, Ψ(m) loss, and apoptosis were suppressed in cells co-treated with a specific inhibitor of casein kinase II (CK II) (4,5,6,7-tetrabromobenzotriazole). Small interfering RNA (siRNA)-mediated suppression of BIK inhibited GA-induced oligomeric complex of BAX/BAK in the ER and mitochondria, increase of cytosolic Ca(+)(+) and ROS, and apoptosis, but did not attenuate the increase in the level of Ser 15-phosphated p53 induced by GA. Blockade of p53 expression by short hairpin RNA suppressed BAX/BAK oligomerization and ER Ca(+)(+)–ROS-associated apoptosis induced by GA but did not affect GA-induced phospho-BIK (Thr 33/Ser 35) levels. Induction of mitochondrial Cyt c release and ROS generation, increased cytosolic Ca(++) level, and apoptosis by GA was attenuated by expression of the BAX or BAK siRNA. Over-expression of BCL-2 (but not BCL-X(L)) inhibited formation of ER oligomeric BAX/BAK by GA. Our results demonstrated that activation of the CK II by GA is required for the BIK-mediated ROS-dependent apoptotic activity of ER-associated BAX/BAK. |
format | Online Article Text |
id | pubmed-5627504 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-56275042017-10-13 Activation of Casein Kinase II by Gallic Acid Induces BIK–BAX/BAK-Mediated ER Ca(++)-ROS-Dependent Apoptosis of Human Oral Cancer Cells Lin, Meng-Liang Chen, Shih-Shun Front Physiol Physiology Induction of the generation of endoplasmic reticulum (ER) calcium (Ca(++))-mediated reactive oxygen species (ROS) by gallic acid (GA) has been implicated in the mitochondrial apoptotic death of human oral cancer (OC) cells, but the molecular mechanism by which GA causes ER Ca(++) release of OC cells to undergo cell death remains unclear. Here, we report that GA-induced phosphorylation of B-cell lymphoma 2 (BCL-2)-interacting killer (BIK) (threonine (Thr) 33/Serine (Ser) 35) and p53 (Ser 15 and Ser 392), Bcl-2-associated x protein (BAX)/BCL-2 antagonist killer 1 (BAK) oligomerization on the ER and mitochondria, rising of cytosolic Ca(+)(+) and ROS, cytochrome c (Cyt c) release from the mitochondria, Ψ(m) loss, and apoptosis were suppressed in cells co-treated with a specific inhibitor of casein kinase II (CK II) (4,5,6,7-tetrabromobenzotriazole). Small interfering RNA (siRNA)-mediated suppression of BIK inhibited GA-induced oligomeric complex of BAX/BAK in the ER and mitochondria, increase of cytosolic Ca(+)(+) and ROS, and apoptosis, but did not attenuate the increase in the level of Ser 15-phosphated p53 induced by GA. Blockade of p53 expression by short hairpin RNA suppressed BAX/BAK oligomerization and ER Ca(+)(+)–ROS-associated apoptosis induced by GA but did not affect GA-induced phospho-BIK (Thr 33/Ser 35) levels. Induction of mitochondrial Cyt c release and ROS generation, increased cytosolic Ca(++) level, and apoptosis by GA was attenuated by expression of the BAX or BAK siRNA. Over-expression of BCL-2 (but not BCL-X(L)) inhibited formation of ER oligomeric BAX/BAK by GA. Our results demonstrated that activation of the CK II by GA is required for the BIK-mediated ROS-dependent apoptotic activity of ER-associated BAX/BAK. Frontiers Media S.A. 2017-09-29 /pmc/articles/PMC5627504/ /pubmed/29033852 http://dx.doi.org/10.3389/fphys.2017.00761 Text en Copyright © 2017 Lin and Chen. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Physiology Lin, Meng-Liang Chen, Shih-Shun Activation of Casein Kinase II by Gallic Acid Induces BIK–BAX/BAK-Mediated ER Ca(++)-ROS-Dependent Apoptosis of Human Oral Cancer Cells |
title | Activation of Casein Kinase II by Gallic Acid Induces BIK–BAX/BAK-Mediated ER Ca(++)-ROS-Dependent Apoptosis of Human Oral Cancer Cells |
title_full | Activation of Casein Kinase II by Gallic Acid Induces BIK–BAX/BAK-Mediated ER Ca(++)-ROS-Dependent Apoptosis of Human Oral Cancer Cells |
title_fullStr | Activation of Casein Kinase II by Gallic Acid Induces BIK–BAX/BAK-Mediated ER Ca(++)-ROS-Dependent Apoptosis of Human Oral Cancer Cells |
title_full_unstemmed | Activation of Casein Kinase II by Gallic Acid Induces BIK–BAX/BAK-Mediated ER Ca(++)-ROS-Dependent Apoptosis of Human Oral Cancer Cells |
title_short | Activation of Casein Kinase II by Gallic Acid Induces BIK–BAX/BAK-Mediated ER Ca(++)-ROS-Dependent Apoptosis of Human Oral Cancer Cells |
title_sort | activation of casein kinase ii by gallic acid induces bik–bax/bak-mediated er ca(++)-ros-dependent apoptosis of human oral cancer cells |
topic | Physiology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5627504/ https://www.ncbi.nlm.nih.gov/pubmed/29033852 http://dx.doi.org/10.3389/fphys.2017.00761 |
work_keys_str_mv | AT linmengliang activationofcaseinkinaseiibygallicacidinducesbikbaxbakmediatedercarosdependentapoptosisofhumanoralcancercells AT chenshihshun activationofcaseinkinaseiibygallicacidinducesbikbaxbakmediatedercarosdependentapoptosisofhumanoralcancercells |