The conformation change of Bcl-2 is involved in arsenic trioxide-induced apoptosis and inhibition of proliferation in SGC7901 human gastric cancer cells
<p>Abstract</p> <p>Background</p> <p>Arsenic trioxide has been established as a first-line agent for treating acute promyelocytic leukemia. Experimental data suggest that arsenic trioxide also can have a potential use as chemotherapeutic agent for other malignancies. Th...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
BMC
2010-04-01
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| Series: | World Journal of Surgical Oncology |
| Online Access: | http://www.wjso.com/content/8/1/31 |
| _version_ | 1828230411134697472 |
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| author | Li Qiu Ye Aifang Zhou Mengtao Zheng Yihu Bai Yongheng Zhang Qiyu |
| author_facet | Li Qiu Ye Aifang Zhou Mengtao Zheng Yihu Bai Yongheng Zhang Qiyu |
| author_sort | Li Qiu |
| collection | DOAJ |
| description | <p>Abstract</p> <p>Background</p> <p>Arsenic trioxide has been established as a first-line agent for treating acute promyelocytic leukemia. Experimental data suggest that arsenic trioxide also can have a potential use as chemotherapeutic agent for other malignancies. The precise mechanisms of action of arsenic trioxide have though not been elucidated. As the role of Bcl-2 in arsenic trioxide-mediated cell apoptosis and conformation change of Bcl-2 in response to arsenic trioxide treatment has not been studied. The aim of the present study was to determine whether conformation change of Bcl-2 is involved in the action of arsenic trioxide.</p> <p>Methods</p> <p>Human gastric cancer SGC7901 cells were exposed to different concentrations of arsenic trioxide. Proliferation was measured by using the Kit-8 cell counting assay. Analysis of nuclear morphology was observed by DAPI staining. The apoptosis rates of cells treated with arsenic trioxide were analyzed by flow cytometry using Annexin V-FITC staining. The conformation change of Bcl-2 and Bax activation were detected by immunostaining and Western blot analysis. Total expression of Bcl-2 and Bax were examined by Western blot analysis.</p> <p>Results</p> <p>Arsenic trioxide inhibited the growth of human gastric cancer SGC7901 cells and induced apoptosis. There were two Bcl-2 phenotypes coexisting in SGC7901 cells and the Bcl-2 cytoprotective phenotype could change into a cytodestructive phenotype following conformational change of Bcl-2, triggered by arsenic trioxide exposure. Bax activation might also be involved in arsenic trioxide-induced Bcl-2 conformational change. Arsenic trioxide did not change levels of total Bcl-2 expression, but up-regulated total Bax expression for the treatment time ranging from 3 to 24 hours.</p> <p>Conclusion</p> <p>Arsenic trioxide induces apoptosis through induction of Bcl-2 conformational change, Bax activation and up-regulation of total Bax expression rather than affecting total Bcl-2 expression in human gastric cancer SGC7901 cells. The conformational change of Bcl-2 may be a novel described mechanism of arsenic trioxide-induced apoptosis in cancer cells.</p> |
| first_indexed | 2024-04-12T18:48:05Z |
| format | Article |
| id | doaj.art-766fe5c64c6b4f378cfa8ae8506cbc47 |
| institution | Directory Open Access Journal |
| issn | 1477-7819 |
| language | English |
| last_indexed | 2024-04-12T18:48:05Z |
| publishDate | 2010-04-01 |
| publisher | BMC |
| record_format | Article |
| series | World Journal of Surgical Oncology |
| spelling | doaj.art-766fe5c64c6b4f378cfa8ae8506cbc472022-12-22T03:20:33ZengBMCWorld Journal of Surgical Oncology1477-78192010-04-01813110.1186/1477-7819-8-31The conformation change of Bcl-2 is involved in arsenic trioxide-induced apoptosis and inhibition of proliferation in SGC7901 human gastric cancer cellsLi QiuYe AifangZhou MengtaoZheng YihuBai YonghengZhang Qiyu<p>Abstract</p> <p>Background</p> <p>Arsenic trioxide has been established as a first-line agent for treating acute promyelocytic leukemia. Experimental data suggest that arsenic trioxide also can have a potential use as chemotherapeutic agent for other malignancies. The precise mechanisms of action of arsenic trioxide have though not been elucidated. As the role of Bcl-2 in arsenic trioxide-mediated cell apoptosis and conformation change of Bcl-2 in response to arsenic trioxide treatment has not been studied. The aim of the present study was to determine whether conformation change of Bcl-2 is involved in the action of arsenic trioxide.</p> <p>Methods</p> <p>Human gastric cancer SGC7901 cells were exposed to different concentrations of arsenic trioxide. Proliferation was measured by using the Kit-8 cell counting assay. Analysis of nuclear morphology was observed by DAPI staining. The apoptosis rates of cells treated with arsenic trioxide were analyzed by flow cytometry using Annexin V-FITC staining. The conformation change of Bcl-2 and Bax activation were detected by immunostaining and Western blot analysis. Total expression of Bcl-2 and Bax were examined by Western blot analysis.</p> <p>Results</p> <p>Arsenic trioxide inhibited the growth of human gastric cancer SGC7901 cells and induced apoptosis. There were two Bcl-2 phenotypes coexisting in SGC7901 cells and the Bcl-2 cytoprotective phenotype could change into a cytodestructive phenotype following conformational change of Bcl-2, triggered by arsenic trioxide exposure. Bax activation might also be involved in arsenic trioxide-induced Bcl-2 conformational change. Arsenic trioxide did not change levels of total Bcl-2 expression, but up-regulated total Bax expression for the treatment time ranging from 3 to 24 hours.</p> <p>Conclusion</p> <p>Arsenic trioxide induces apoptosis through induction of Bcl-2 conformational change, Bax activation and up-regulation of total Bax expression rather than affecting total Bcl-2 expression in human gastric cancer SGC7901 cells. The conformational change of Bcl-2 may be a novel described mechanism of arsenic trioxide-induced apoptosis in cancer cells.</p>http://www.wjso.com/content/8/1/31 |
| spellingShingle | Li Qiu Ye Aifang Zhou Mengtao Zheng Yihu Bai Yongheng Zhang Qiyu The conformation change of Bcl-2 is involved in arsenic trioxide-induced apoptosis and inhibition of proliferation in SGC7901 human gastric cancer cells World Journal of Surgical Oncology |
| title | The conformation change of Bcl-2 is involved in arsenic trioxide-induced apoptosis and inhibition of proliferation in SGC7901 human gastric cancer cells |
| title_full | The conformation change of Bcl-2 is involved in arsenic trioxide-induced apoptosis and inhibition of proliferation in SGC7901 human gastric cancer cells |
| title_fullStr | The conformation change of Bcl-2 is involved in arsenic trioxide-induced apoptosis and inhibition of proliferation in SGC7901 human gastric cancer cells |
| title_full_unstemmed | The conformation change of Bcl-2 is involved in arsenic trioxide-induced apoptosis and inhibition of proliferation in SGC7901 human gastric cancer cells |
| title_short | The conformation change of Bcl-2 is involved in arsenic trioxide-induced apoptosis and inhibition of proliferation in SGC7901 human gastric cancer cells |
| title_sort | conformation change of bcl 2 is involved in arsenic trioxide induced apoptosis and inhibition of proliferation in sgc7901 human gastric cancer cells |
| url | http://www.wjso.com/content/8/1/31 |
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