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 to...
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Frontiers Media S.A.
2017-09-01
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| Series: | Frontiers in Physiology |
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| Online Access: | http://journal.frontiersin.org/article/10.3389/fphys.2017.00761/full |
| _version_ | 1828490905999376384 |
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| author | Meng-Liang Lin Shih-Shun Chen |
| author_facet | Meng-Liang Lin Shih-Shun Chen |
| author_sort | Meng-Liang Lin |
| collection | DOAJ |
| 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, Ψm 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-XL) 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. |
| first_indexed | 2024-12-11T10:52:52Z |
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| issn | 1664-042X |
| language | English |
| last_indexed | 2024-12-11T10:52:52Z |
| publishDate | 2017-09-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Physiology |
| spelling | doaj.art-ecba5ce2e7d944c4945e15ce1c222b832022-12-22T01:10:13ZengFrontiers Media S.A.Frontiers in Physiology1664-042X2017-09-01810.3389/fphys.2017.00761295175Activation of Casein Kinase II by Gallic Acid Induces BIK–BAX/BAK-Mediated ER Ca++-ROS-Dependent Apoptosis of Human Oral Cancer CellsMeng-Liang Lin0Shih-Shun Chen1Department of Medical Laboratory Science and Biotechnology, China Medical University, Taichung, TaiwanDepartment of Medical Laboratory Science and Biotechnology, Central Taiwan University of Science and Technology, Taichung, TaiwanInduction 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, Ψm 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-XL) 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.http://journal.frontiersin.org/article/10.3389/fphys.2017.00761/fullBAX/BAKBIKcasein kinase IIER Ca++gallic acidROS |
| spellingShingle | Meng-Liang Lin Shih-Shun Chen Activation of Casein Kinase II by Gallic Acid Induces BIK–BAX/BAK-Mediated ER Ca++-ROS-Dependent Apoptosis of Human Oral Cancer Cells Frontiers in Physiology BAX/BAK BIK casein kinase II ER Ca++ gallic acid ROS |
| 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 | BAX/BAK BIK casein kinase II ER Ca++ gallic acid ROS |
| url | http://journal.frontiersin.org/article/10.3389/fphys.2017.00761/full |
| work_keys_str_mv | AT menglianglin activationofcaseinkinaseiibygallicacidinducesbikbaxbakmediatedercarosdependentapoptosisofhumanoralcancercells AT shihshunchen activationofcaseinkinaseiibygallicacidinducesbikbaxbakmediatedercarosdependentapoptosisofhumanoralcancercells |