Toxicarioside A inhibits tumor growth and angiogenesis: involvement of TGF-β/endoglin signaling.
Toxicarioside A is a cardenolide isolated mainly from plants and animals. Emerging evidence demonstrate that cardenolides not only have cardiac effects but also anticancer effects. In this study, we used in vivo models to investigate the antitumor activities of toxicarioside A and the potential mech...
| 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/PMC3508932?pdf=render |
| _version_ | 1828973043580403712 |
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| author | Feng-Ying Huang Wen-Li Mei Yue-Nan Li Guang-Hong Tan Hao-Fu Dai Jun-Li Guo Hua Wang Yong-Hao Huang Huan-Ge Zhao Song-Lin Zhou Ying-Ying Lin |
| author_facet | Feng-Ying Huang Wen-Li Mei Yue-Nan Li Guang-Hong Tan Hao-Fu Dai Jun-Li Guo Hua Wang Yong-Hao Huang Huan-Ge Zhao Song-Lin Zhou Ying-Ying Lin |
| author_sort | Feng-Ying Huang |
| collection | DOAJ |
| description | Toxicarioside A is a cardenolide isolated mainly from plants and animals. Emerging evidence demonstrate that cardenolides not only have cardiac effects but also anticancer effects. In this study, we used in vivo models to investigate the antitumor activities of toxicarioside A and the potential mechanisms behind them. Murine colorectal carcinoma (CT26) and Lewis lung carcinoma (LL/2) models were established in syngeneic BALB/c and C57BL/6 mice, respectively. We found that the optimum effective dose of toxicarioside A treatment significantly suppressed tumor growth and angiogenesis in CT and LL/2 tumor models in vivo. Northern and Western blot analysis showed significant inhibition of endoglin expression in toxicarioside A-treated human umbilical vein endothelial cells (HUVECs) in vitro and tumor tissues in vivo. Toxicarioside A treatment significantly inhibited cell proliferation, migration and invasion, but did not cause significant cell apoptosis and affected other membrane protein (such as CD31 and MHC I) expression. In addition, TGF-β expression was also significantly inhibited in CT26 and LL/2 tumor cells treated with toxicarioside A. Western blot analysis indicated that Smad1 and phosphorylated Smad1 but not Smad2/3 and phosphorylated Smad2/3 were attenuated in HUVECs treated with toxicarioside A. Smad1 and Smad2/3 signaling remained unchanged in CT26 and LL/2 tumor cells treated with toxicarioside A. Endoglin knockout by small interfering RNA against endoglin induced alternations in Smad1 and Smad2/3 signaling in HUVECs. Our results indicate that toxicarioside A suppresses tumor growth through inhibition of endoglin-related tumor angiogenesis, which involves in the endoglin/TGF-β signal pathway. |
| first_indexed | 2024-12-14T13:39:27Z |
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| id | doaj.art-b926181cd6434a9ea0919349abadd3db |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-14T13:39:27Z |
| publishDate | 2012-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-b926181cd6434a9ea0919349abadd3db2022-12-21T22:59:29ZengPublic Library of Science (PLoS)PLoS ONE1932-62032012-01-01711e5035110.1371/journal.pone.0050351Toxicarioside A inhibits tumor growth and angiogenesis: involvement of TGF-β/endoglin signaling.Feng-Ying HuangWen-Li MeiYue-Nan LiGuang-Hong TanHao-Fu DaiJun-Li GuoHua WangYong-Hao HuangHuan-Ge ZhaoSong-Lin ZhouYing-Ying LinToxicarioside A is a cardenolide isolated mainly from plants and animals. Emerging evidence demonstrate that cardenolides not only have cardiac effects but also anticancer effects. In this study, we used in vivo models to investigate the antitumor activities of toxicarioside A and the potential mechanisms behind them. Murine colorectal carcinoma (CT26) and Lewis lung carcinoma (LL/2) models were established in syngeneic BALB/c and C57BL/6 mice, respectively. We found that the optimum effective dose of toxicarioside A treatment significantly suppressed tumor growth and angiogenesis in CT and LL/2 tumor models in vivo. Northern and Western blot analysis showed significant inhibition of endoglin expression in toxicarioside A-treated human umbilical vein endothelial cells (HUVECs) in vitro and tumor tissues in vivo. Toxicarioside A treatment significantly inhibited cell proliferation, migration and invasion, but did not cause significant cell apoptosis and affected other membrane protein (such as CD31 and MHC I) expression. In addition, TGF-β expression was also significantly inhibited in CT26 and LL/2 tumor cells treated with toxicarioside A. Western blot analysis indicated that Smad1 and phosphorylated Smad1 but not Smad2/3 and phosphorylated Smad2/3 were attenuated in HUVECs treated with toxicarioside A. Smad1 and Smad2/3 signaling remained unchanged in CT26 and LL/2 tumor cells treated with toxicarioside A. Endoglin knockout by small interfering RNA against endoglin induced alternations in Smad1 and Smad2/3 signaling in HUVECs. Our results indicate that toxicarioside A suppresses tumor growth through inhibition of endoglin-related tumor angiogenesis, which involves in the endoglin/TGF-β signal pathway.http://europepmc.org/articles/PMC3508932?pdf=render |
| spellingShingle | Feng-Ying Huang Wen-Li Mei Yue-Nan Li Guang-Hong Tan Hao-Fu Dai Jun-Li Guo Hua Wang Yong-Hao Huang Huan-Ge Zhao Song-Lin Zhou Ying-Ying Lin Toxicarioside A inhibits tumor growth and angiogenesis: involvement of TGF-β/endoglin signaling. PLoS ONE |
| title | Toxicarioside A inhibits tumor growth and angiogenesis: involvement of TGF-β/endoglin signaling. |
| title_full | Toxicarioside A inhibits tumor growth and angiogenesis: involvement of TGF-β/endoglin signaling. |
| title_fullStr | Toxicarioside A inhibits tumor growth and angiogenesis: involvement of TGF-β/endoglin signaling. |
| title_full_unstemmed | Toxicarioside A inhibits tumor growth and angiogenesis: involvement of TGF-β/endoglin signaling. |
| title_short | Toxicarioside A inhibits tumor growth and angiogenesis: involvement of TGF-β/endoglin signaling. |
| title_sort | toxicarioside a inhibits tumor growth and angiogenesis involvement of tgf β endoglin signaling |
| url | http://europepmc.org/articles/PMC3508932?pdf=render |
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