Calpain/SHP-1 interaction by honokiol dampening peritoneal dissemination of gastric cancer in nu/nu mice.
BACKGROUND: Honokiol, a small-molecular weight natural product, has previously been reported to activate apoptosis and inhibit gastric tumorigenesis. Whether honokiol inhibits the angiogenesis and metastasis of gastric cancer cells remains unknown. METHODOLOGY/PRINCIPAL FINDINGS: We tested the effec...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2012-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3427156?pdf=render |
| _version_ | 1818506877189750784 |
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| author | Shing Hwa Liu Keh Bin Wang Keng Hsin Lan Wen Jane Lee Hung Chuan Pan Sheng Mao Wu Yen Chun Peng Yi Ching Chen Chin Chang Shen Hsu Chen Cheng Ko Kaung Liao Meei Ling Sheu |
| author_facet | Shing Hwa Liu Keh Bin Wang Keng Hsin Lan Wen Jane Lee Hung Chuan Pan Sheng Mao Wu Yen Chun Peng Yi Ching Chen Chin Chang Shen Hsu Chen Cheng Ko Kaung Liao Meei Ling Sheu |
| author_sort | Shing Hwa Liu |
| collection | DOAJ |
| description | BACKGROUND: Honokiol, a small-molecular weight natural product, has previously been reported to activate apoptosis and inhibit gastric tumorigenesis. Whether honokiol inhibits the angiogenesis and metastasis of gastric cancer cells remains unknown. METHODOLOGY/PRINCIPAL FINDINGS: We tested the effects of honokiol on angiogenic activity and peritoneal dissemination using in vivo, ex vivo and in vitro assay systems. The signaling responses in human gastric cancer cells, human umbilical vascular endothelial cells (HUVECs), and isolated tumors were detected and analyzed. In a xenograft gastric tumor mouse model, honokiol significantly inhibited the peritoneal dissemination detected by PET/CT technique. Honokiol also effectively attenuated the angiogenesis detected by chick chorioallantoic membrane assay, mouse matrigel plug assay, rat aortic ring endothelial cell sprouting assay, and endothelial cell tube formation assay. Furthermore, honokiol effectively enhanced signal transducer and activator of transcription (STAT-3) dephosphorylation and inhibited STAT-3 DNA binding activity in human gastric cancer cells and HUVECs, which was correlated with the up-regulation of the activity and protein expression of Src homology 2 (SH2)-containing tyrosine phosphatase-1 (SHP-1). Calpain-II inhibitor and siRNA transfection significantly reversed the honokiol-induced SHP-1 activity. The decreased STAT-3 phosphorylation and increased SHP-1 expression were also shown in isolated peritoneal metastatic tumors. Honokiol was also capable of inhibiting VEGF generation, which could be reversed by SHP-1 siRNA transfection. CONCLUSIONS/SIGNIFICANCE: Honokiol increases expression and activity of SPH-1 that further deactivates STAT3 pathway. These findings also suggest that honokiol is a novel and potent inhibitor of angiogenesis and peritoneal dissemination of gastric cancer cells, providing support for the application potential of honokiol in gastric cancer therapy. |
| first_indexed | 2024-12-10T22:10:38Z |
| format | Article |
| id | doaj.art-46e5b054d55e479b956cbc39c3f306ce |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-10T22:10:38Z |
| publishDate | 2012-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-46e5b054d55e479b956cbc39c3f306ce2022-12-22T01:31:36ZengPublic Library of Science (PLoS)PLoS ONE1932-62032012-01-0178e4371110.1371/journal.pone.0043711Calpain/SHP-1 interaction by honokiol dampening peritoneal dissemination of gastric cancer in nu/nu mice.Shing Hwa LiuKeh Bin WangKeng Hsin LanWen Jane LeeHung Chuan PanSheng Mao WuYen Chun PengYi Ching ChenChin Chang ShenHsu Chen ChengKo Kaung LiaoMeei Ling SheuBACKGROUND: Honokiol, a small-molecular weight natural product, has previously been reported to activate apoptosis and inhibit gastric tumorigenesis. Whether honokiol inhibits the angiogenesis and metastasis of gastric cancer cells remains unknown. METHODOLOGY/PRINCIPAL FINDINGS: We tested the effects of honokiol on angiogenic activity and peritoneal dissemination using in vivo, ex vivo and in vitro assay systems. The signaling responses in human gastric cancer cells, human umbilical vascular endothelial cells (HUVECs), and isolated tumors were detected and analyzed. In a xenograft gastric tumor mouse model, honokiol significantly inhibited the peritoneal dissemination detected by PET/CT technique. Honokiol also effectively attenuated the angiogenesis detected by chick chorioallantoic membrane assay, mouse matrigel plug assay, rat aortic ring endothelial cell sprouting assay, and endothelial cell tube formation assay. Furthermore, honokiol effectively enhanced signal transducer and activator of transcription (STAT-3) dephosphorylation and inhibited STAT-3 DNA binding activity in human gastric cancer cells and HUVECs, which was correlated with the up-regulation of the activity and protein expression of Src homology 2 (SH2)-containing tyrosine phosphatase-1 (SHP-1). Calpain-II inhibitor and siRNA transfection significantly reversed the honokiol-induced SHP-1 activity. The decreased STAT-3 phosphorylation and increased SHP-1 expression were also shown in isolated peritoneal metastatic tumors. Honokiol was also capable of inhibiting VEGF generation, which could be reversed by SHP-1 siRNA transfection. CONCLUSIONS/SIGNIFICANCE: Honokiol increases expression and activity of SPH-1 that further deactivates STAT3 pathway. These findings also suggest that honokiol is a novel and potent inhibitor of angiogenesis and peritoneal dissemination of gastric cancer cells, providing support for the application potential of honokiol in gastric cancer therapy.http://europepmc.org/articles/PMC3427156?pdf=render |
| spellingShingle | Shing Hwa Liu Keh Bin Wang Keng Hsin Lan Wen Jane Lee Hung Chuan Pan Sheng Mao Wu Yen Chun Peng Yi Ching Chen Chin Chang Shen Hsu Chen Cheng Ko Kaung Liao Meei Ling Sheu Calpain/SHP-1 interaction by honokiol dampening peritoneal dissemination of gastric cancer in nu/nu mice. PLoS ONE |
| title | Calpain/SHP-1 interaction by honokiol dampening peritoneal dissemination of gastric cancer in nu/nu mice. |
| title_full | Calpain/SHP-1 interaction by honokiol dampening peritoneal dissemination of gastric cancer in nu/nu mice. |
| title_fullStr | Calpain/SHP-1 interaction by honokiol dampening peritoneal dissemination of gastric cancer in nu/nu mice. |
| title_full_unstemmed | Calpain/SHP-1 interaction by honokiol dampening peritoneal dissemination of gastric cancer in nu/nu mice. |
| title_short | Calpain/SHP-1 interaction by honokiol dampening peritoneal dissemination of gastric cancer in nu/nu mice. |
| title_sort | calpain shp 1 interaction by honokiol dampening peritoneal dissemination of gastric cancer in nu nu mice |
| url | http://europepmc.org/articles/PMC3427156?pdf=render |
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