Suppression of growth, migration and invasion of highly-metastatic human breast cancer cells by berbamine and its molecular mechanisms of action
<p>Abstract</p> <p>Background</p> <p>Breast cancer is the second leading cause of cancer related deaths among females worldwide. Berbamine (BER), a kind of bis-benzylisoquinoline alkaloid, has been used to treat clinical patients with inflammation and cancer for many ye...
| Main Authors: | , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2009-10-01
|
| Series: | Molecular Cancer |
| Online Access: | http://www.molecular-cancer.com/content/8/1/81 |
| _version_ | 1811251190426501120 |
|---|---|
| author | Wang Fengfei Lu Zhaoqiao Duan Huiying Luan Jinling Liu Kun Yu Pengfei Liu Ke Zhang Ying Liu Qian Wang Shan Wu Erxi Yagasaki Kazumi Zhang Guoying |
| author_facet | Wang Fengfei Lu Zhaoqiao Duan Huiying Luan Jinling Liu Kun Yu Pengfei Liu Ke Zhang Ying Liu Qian Wang Shan Wu Erxi Yagasaki Kazumi Zhang Guoying |
| author_sort | Wang Fengfei |
| collection | DOAJ |
| description | <p>Abstract</p> <p>Background</p> <p>Breast cancer is the second leading cause of cancer related deaths among females worldwide. Berbamine (BER), a kind of bis-benzylisoquinoline alkaloid, has been used to treat clinical patients with inflammation and cancer for many years in China. The purpose of this study is to investigate the activity of BER against highly-metastatic human breast cancer and its molecular mechanisms of action.</p> <p>Results</p> <p>In our study, we found that BER inhibits growth of highly-metastatic human breast cancer cell lines MDA-MB-231 and MDA-MB-435S cells dose-dependently and time-dependently. The sera from BER-treated rats suppress the growth of MDA-MB-231 cells. BER shows synergistic effects with some existing anticancer agents such as trichostatin A (TSA, the histone deacetylase inhibitor), celecoxib (the inhibitor of COX-2), and carmofur against the growth of MDA-MB-231 cells. BER also displays the strong activity of inducing apoptosis in both estrogen receptor-negative MDA-MB-231 cells and estrogen receptor-alpha-positive MCF-7 breast cancer cells, but not in normal human mammary epithelial cell line MCF10A. BER down-regulates anti-apoptotic protein Bcl-2 levels and up-regulates pro-apoptotic protein Bax expressions in MDA-MB-231 and MDA-MB-435S cells. BER also has synergistic effects with anticancer agents trichostatin A, celecoxib and/or carmofur on reducing Bcl-2/Bax ratios and VEGF secretions in MDA-MB-231 cells. In addition, BER significantly suppresses cell migration and invasion, as well as decreases pro-MMP-9/pro-MMP-2 activation in breast cancer cells. Furthermore, BER suppresses Akt and nuclear factor <it>κ</it>B signaling by reducing the phosphorylation of c-Met and Akt, and inhibiting their downstream targets such as nuclear factor <it>κ</it>B p-65, Bcl-2/Bax, osteopontin, VEGF, MMP-9 and MMP-2 on protein and/or mRNA levels in breast cancer cells.</p> <p>Conclusion</p> <p>Our findings have showed that BER suppresses the growth, migration and invasion in highly-metastatic human breast cancer cells by possibly inhibiting Akt and NF-<it>κ</it>B signaling with their upstream target c-Met and downstream targets Bcl-2/Bax, osteopontin, VEGF, MMP-9 and MMP-2. BER has synergistic effects with anticancer agents trichostatin A, celecoxib and carmofur on inhibiting the growth of MDA-MB-231 cells and reducing the ratio of Bcl-2/Bax and/or VEGF expressions in the cancer cells. These findings suggest that BER may have the wide therapeutic and/or adjuvant therapeutic application in the treatment of human breast cancer and other cancers.</p> |
| first_indexed | 2024-04-12T16:15:53Z |
| format | Article |
| id | doaj.art-dd876bad652941f38551361d8b1ccd40 |
| institution | Directory Open Access Journal |
| issn | 1476-4598 |
| language | English |
| last_indexed | 2024-04-12T16:15:53Z |
| publishDate | 2009-10-01 |
| publisher | BMC |
| record_format | Article |
| series | Molecular Cancer |
| spelling | doaj.art-dd876bad652941f38551361d8b1ccd402022-12-22T03:25:43ZengBMCMolecular Cancer1476-45982009-10-01818110.1186/1476-4598-8-81Suppression of growth, migration and invasion of highly-metastatic human breast cancer cells by berbamine and its molecular mechanisms of actionWang FengfeiLu ZhaoqiaoDuan HuiyingLuan JinlingLiu KunYu PengfeiLiu KeZhang YingLiu QianWang ShanWu ErxiYagasaki KazumiZhang Guoying<p>Abstract</p> <p>Background</p> <p>Breast cancer is the second leading cause of cancer related deaths among females worldwide. Berbamine (BER), a kind of bis-benzylisoquinoline alkaloid, has been used to treat clinical patients with inflammation and cancer for many years in China. The purpose of this study is to investigate the activity of BER against highly-metastatic human breast cancer and its molecular mechanisms of action.</p> <p>Results</p> <p>In our study, we found that BER inhibits growth of highly-metastatic human breast cancer cell lines MDA-MB-231 and MDA-MB-435S cells dose-dependently and time-dependently. The sera from BER-treated rats suppress the growth of MDA-MB-231 cells. BER shows synergistic effects with some existing anticancer agents such as trichostatin A (TSA, the histone deacetylase inhibitor), celecoxib (the inhibitor of COX-2), and carmofur against the growth of MDA-MB-231 cells. BER also displays the strong activity of inducing apoptosis in both estrogen receptor-negative MDA-MB-231 cells and estrogen receptor-alpha-positive MCF-7 breast cancer cells, but not in normal human mammary epithelial cell line MCF10A. BER down-regulates anti-apoptotic protein Bcl-2 levels and up-regulates pro-apoptotic protein Bax expressions in MDA-MB-231 and MDA-MB-435S cells. BER also has synergistic effects with anticancer agents trichostatin A, celecoxib and/or carmofur on reducing Bcl-2/Bax ratios and VEGF secretions in MDA-MB-231 cells. In addition, BER significantly suppresses cell migration and invasion, as well as decreases pro-MMP-9/pro-MMP-2 activation in breast cancer cells. Furthermore, BER suppresses Akt and nuclear factor <it>κ</it>B signaling by reducing the phosphorylation of c-Met and Akt, and inhibiting their downstream targets such as nuclear factor <it>κ</it>B p-65, Bcl-2/Bax, osteopontin, VEGF, MMP-9 and MMP-2 on protein and/or mRNA levels in breast cancer cells.</p> <p>Conclusion</p> <p>Our findings have showed that BER suppresses the growth, migration and invasion in highly-metastatic human breast cancer cells by possibly inhibiting Akt and NF-<it>κ</it>B signaling with their upstream target c-Met and downstream targets Bcl-2/Bax, osteopontin, VEGF, MMP-9 and MMP-2. BER has synergistic effects with anticancer agents trichostatin A, celecoxib and carmofur on inhibiting the growth of MDA-MB-231 cells and reducing the ratio of Bcl-2/Bax and/or VEGF expressions in the cancer cells. These findings suggest that BER may have the wide therapeutic and/or adjuvant therapeutic application in the treatment of human breast cancer and other cancers.</p>http://www.molecular-cancer.com/content/8/1/81 |
| spellingShingle | Wang Fengfei Lu Zhaoqiao Duan Huiying Luan Jinling Liu Kun Yu Pengfei Liu Ke Zhang Ying Liu Qian Wang Shan Wu Erxi Yagasaki Kazumi Zhang Guoying Suppression of growth, migration and invasion of highly-metastatic human breast cancer cells by berbamine and its molecular mechanisms of action Molecular Cancer |
| title | Suppression of growth, migration and invasion of highly-metastatic human breast cancer cells by berbamine and its molecular mechanisms of action |
| title_full | Suppression of growth, migration and invasion of highly-metastatic human breast cancer cells by berbamine and its molecular mechanisms of action |
| title_fullStr | Suppression of growth, migration and invasion of highly-metastatic human breast cancer cells by berbamine and its molecular mechanisms of action |
| title_full_unstemmed | Suppression of growth, migration and invasion of highly-metastatic human breast cancer cells by berbamine and its molecular mechanisms of action |
| title_short | Suppression of growth, migration and invasion of highly-metastatic human breast cancer cells by berbamine and its molecular mechanisms of action |
| title_sort | suppression of growth migration and invasion of highly metastatic human breast cancer cells by berbamine and its molecular mechanisms of action |
| url | http://www.molecular-cancer.com/content/8/1/81 |
| work_keys_str_mv | AT wangfengfei suppressionofgrowthmigrationandinvasionofhighlymetastatichumanbreastcancercellsbyberbamineanditsmolecularmechanismsofaction AT luzhaoqiao suppressionofgrowthmigrationandinvasionofhighlymetastatichumanbreastcancercellsbyberbamineanditsmolecularmechanismsofaction AT duanhuiying suppressionofgrowthmigrationandinvasionofhighlymetastatichumanbreastcancercellsbyberbamineanditsmolecularmechanismsofaction AT luanjinling suppressionofgrowthmigrationandinvasionofhighlymetastatichumanbreastcancercellsbyberbamineanditsmolecularmechanismsofaction AT liukun suppressionofgrowthmigrationandinvasionofhighlymetastatichumanbreastcancercellsbyberbamineanditsmolecularmechanismsofaction AT yupengfei suppressionofgrowthmigrationandinvasionofhighlymetastatichumanbreastcancercellsbyberbamineanditsmolecularmechanismsofaction AT liuke suppressionofgrowthmigrationandinvasionofhighlymetastatichumanbreastcancercellsbyberbamineanditsmolecularmechanismsofaction AT zhangying suppressionofgrowthmigrationandinvasionofhighlymetastatichumanbreastcancercellsbyberbamineanditsmolecularmechanismsofaction AT liuqian suppressionofgrowthmigrationandinvasionofhighlymetastatichumanbreastcancercellsbyberbamineanditsmolecularmechanismsofaction AT wangshan suppressionofgrowthmigrationandinvasionofhighlymetastatichumanbreastcancercellsbyberbamineanditsmolecularmechanismsofaction AT wuerxi suppressionofgrowthmigrationandinvasionofhighlymetastatichumanbreastcancercellsbyberbamineanditsmolecularmechanismsofaction AT yagasakikazumi suppressionofgrowthmigrationandinvasionofhighlymetastatichumanbreastcancercellsbyberbamineanditsmolecularmechanismsofaction AT zhangguoying suppressionofgrowthmigrationandinvasionofhighlymetastatichumanbreastcancercellsbyberbamineanditsmolecularmechanismsofaction |