Thapsigargin Induces Apoptosis by Impairing Cytoskeleton Dynamics in Human Lung Adenocarcinoma Cells
The objective of this study was performed to investigate the effects of thapsigargin on apoptosis, actin cytoskeletal dynamics, and actin cytoskeletal proteins in human lung adenocarcinoma cell. Thapsigargin is a specific irreversible inhibitor of ER calcium-ATPase, which may promote ER stress by de...
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| Format: | Article |
| Language: | English |
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Wiley
2014-01-01
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| Series: | The Scientific World Journal |
| Online Access: | http://dx.doi.org/10.1155/2014/619050 |
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| author | Fei Wang Da-zhong Liu Hao Xu Yi Li Wei Wang Bai-lu Liu Lin-you Zhang |
| author_facet | Fei Wang Da-zhong Liu Hao Xu Yi Li Wei Wang Bai-lu Liu Lin-you Zhang |
| author_sort | Fei Wang |
| collection | DOAJ |
| description | The objective of this study was performed to investigate the effects of thapsigargin on apoptosis, actin cytoskeletal dynamics, and actin cytoskeletal proteins in human lung adenocarcinoma cell. Thapsigargin is a specific irreversible inhibitor of ER calcium-ATPase, which may promote ER stress by depletion of lumenal calcium stores and show potential to induce cell death. The effects of thapsigargin on the apoptosis in A549 cells were assayed by Hoechst staining. Moreover, the F-actin staining by Rhodamine-phalloidin and RhoA antibody for cytoskeleton organizations were applied to A549 cells. To confirm the impairment of cytoskeletal dynamics treated with thapsigargin, western blots were applied to analyze the protein levels of p-Cofilin-1 (Ser3), Cofilin-1, and pPaxillin (Tyr118), as well as RhoA and pS6 (S240/244). Results suggest that thapsigargin may induce cell death in A549 cells with a time- and dose-dependent manner. The F-actin fibers and RhoA signals are also reduced with a time- and dose-dependent manner by thapsigargin treatment. The phosphorylation forms of Cofilin-1 and paxillin are attenuated by 1 μM thapsigargin treatment for 24 h. These alternations may be caused by the inhibition of of mTORC1 activities (indicated by pS6 (Ser240/244)) and RhoA pathways after thapsigargin treatment. The present findings highlight important roles of calcium entry in cytoskeleton organization and apoptosis in human lung adenocarcinoma cells and will help to set a stage to the clinical treatment of cancer cell metastasis. |
| format | Article |
| id | doaj-art-f712f965a5784d09893acc07a6c1c507 |
| institution | Kabale University |
| issn | 2356-6140 1537-744X |
| language | English |
| publishDate | 2014-01-01 |
| publisher | Wiley |
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| series | The Scientific World Journal |
| spelling | doaj-art-f712f965a5784d09893acc07a6c1c5072025-02-03T01:33:24ZengWileyThe Scientific World Journal2356-61401537-744X2014-01-01201410.1155/2014/619050619050Thapsigargin Induces Apoptosis by Impairing Cytoskeleton Dynamics in Human Lung Adenocarcinoma CellsFei Wang0Da-zhong Liu1Hao Xu2Yi Li3Wei Wang4Bai-lu Liu5Lin-you Zhang6Department of Thoracic Surgery, The Second Affiliated Hospital of Harbin Medical University, No. 246 Xuefu, Nangang District, Harbin 150086, ChinaDepartment of Thoracic Surgery, The Second Affiliated Hospital of Harbin Medical University, No. 246 Xuefu, Nangang District, Harbin 150086, ChinaDepartment of Thoracic Surgery, The Second Affiliated Hospital of Harbin Medical University, No. 246 Xuefu, Nangang District, Harbin 150086, ChinaDepartment of Thoracic Surgery, The Second Affiliated Hospital of Harbin Medical University, No. 246 Xuefu, Nangang District, Harbin 150086, ChinaDepartment of Thoracic Surgery, The Second Affiliated Hospital of Harbin Medical University, No. 246 Xuefu, Nangang District, Harbin 150086, ChinaDepartment of Computerized Tomography, The Second Affiliated Hospital of Harbin Medical University, No. 246 Xuefu, Nangang District, Harbin 150086, ChinaDepartment of Thoracic Surgery, The Second Affiliated Hospital of Harbin Medical University, No. 246 Xuefu, Nangang District, Harbin 150086, ChinaThe objective of this study was performed to investigate the effects of thapsigargin on apoptosis, actin cytoskeletal dynamics, and actin cytoskeletal proteins in human lung adenocarcinoma cell. Thapsigargin is a specific irreversible inhibitor of ER calcium-ATPase, which may promote ER stress by depletion of lumenal calcium stores and show potential to induce cell death. The effects of thapsigargin on the apoptosis in A549 cells were assayed by Hoechst staining. Moreover, the F-actin staining by Rhodamine-phalloidin and RhoA antibody for cytoskeleton organizations were applied to A549 cells. To confirm the impairment of cytoskeletal dynamics treated with thapsigargin, western blots were applied to analyze the protein levels of p-Cofilin-1 (Ser3), Cofilin-1, and pPaxillin (Tyr118), as well as RhoA and pS6 (S240/244). Results suggest that thapsigargin may induce cell death in A549 cells with a time- and dose-dependent manner. The F-actin fibers and RhoA signals are also reduced with a time- and dose-dependent manner by thapsigargin treatment. The phosphorylation forms of Cofilin-1 and paxillin are attenuated by 1 μM thapsigargin treatment for 24 h. These alternations may be caused by the inhibition of of mTORC1 activities (indicated by pS6 (Ser240/244)) and RhoA pathways after thapsigargin treatment. The present findings highlight important roles of calcium entry in cytoskeleton organization and apoptosis in human lung adenocarcinoma cells and will help to set a stage to the clinical treatment of cancer cell metastasis.http://dx.doi.org/10.1155/2014/619050 |
| spellingShingle | Fei Wang Da-zhong Liu Hao Xu Yi Li Wei Wang Bai-lu Liu Lin-you Zhang Thapsigargin Induces Apoptosis by Impairing Cytoskeleton Dynamics in Human Lung Adenocarcinoma Cells The Scientific World Journal |
| title | Thapsigargin Induces Apoptosis by Impairing Cytoskeleton Dynamics in Human Lung Adenocarcinoma Cells |
| title_full | Thapsigargin Induces Apoptosis by Impairing Cytoskeleton Dynamics in Human Lung Adenocarcinoma Cells |
| title_fullStr | Thapsigargin Induces Apoptosis by Impairing Cytoskeleton Dynamics in Human Lung Adenocarcinoma Cells |
| title_full_unstemmed | Thapsigargin Induces Apoptosis by Impairing Cytoskeleton Dynamics in Human Lung Adenocarcinoma Cells |
| title_short | Thapsigargin Induces Apoptosis by Impairing Cytoskeleton Dynamics in Human Lung Adenocarcinoma Cells |
| title_sort | thapsigargin induces apoptosis by impairing cytoskeleton dynamics in human lung adenocarcinoma cells |
| url | http://dx.doi.org/10.1155/2014/619050 |
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