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An Ethanolic Extract of Ampelopsis Radix Exerts Anti-colorectal Cancer Effects and Potently Inhibits STAT3 Signaling In Vitro
Colorectal cancer (CRC) is a leading cause of cancer-related morbidity and mortality worldwide. Signal transducer and activator of transcription 3 (STAT3) signaling is constantly activated in CRC, and has been proposed as a pathogenic factor and a therapeutic target of CRC. Ampelopsis Radix (AR), a...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5408070/ https://www.ncbi.nlm.nih.gov/pubmed/28503147 http://dx.doi.org/10.3389/fphar.2017.00227 |
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author | Su, Tao Bai, Jing-Xuan Chen, Ying-Jie Wang, Xin-Ning Fu, Xiu-Qiong Li, Ting Guo, Hui Zhu, Pei-Li Wang, Yue Yu, Zhi-Ling |
author_facet | Su, Tao Bai, Jing-Xuan Chen, Ying-Jie Wang, Xin-Ning Fu, Xiu-Qiong Li, Ting Guo, Hui Zhu, Pei-Li Wang, Yue Yu, Zhi-Ling |
author_sort | Su, Tao |
collection | PubMed |
description | Colorectal cancer (CRC) is a leading cause of cancer-related morbidity and mortality worldwide. Signal transducer and activator of transcription 3 (STAT3) signaling is constantly activated in CRC, and has been proposed as a pathogenic factor and a therapeutic target of CRC. Ampelopsis Radix (AR), a traditional Chinese medicinal herb, possesses low toxicity and has long been used clinically for the treatment of cancers including CRC. Some constituents of AR have been reported to exert anti-cancer properties by targeting STAT3. However, the anti-CRC mode and mechanism of action of AR have not been fully elucidated. Here, we investigated the involvement of STAT3 signaling in the anti-CRC effects of AR. Results showed that AR reduced cell viability, induced cell apoptosis, and suppressed cell migration and invasion in human HCT-116 and SW480 CRC cells. Mechanistic studies showed that AR potently suppressed STAT3 and Src phosphorylation, and inhibited STAT3 nuclear localization in cultured CRC cells. AR also downregulated the expression of STAT3 target genes Mcl-1, Bcl-xL, and MMP-2 that are involved in cell survival and mobility. Moreover, the cytotoxic effect of AR was diminished by overexpressing STAT3C, a persistent active variant of STAT3. In conclusion, AR exerted anti-CRC effects in vitro and these effects are at least in part attributed to the inhibition of STAT3 signaling. Our findings provide a molecular justification for the traditional use of AR in treating CRC, and a pharmacological basis for developing AR-derived modern anti-CRC agent(s). |
format | Online Article Text |
id | pubmed-5408070 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-54080702017-05-12 An Ethanolic Extract of Ampelopsis Radix Exerts Anti-colorectal Cancer Effects and Potently Inhibits STAT3 Signaling In Vitro Su, Tao Bai, Jing-Xuan Chen, Ying-Jie Wang, Xin-Ning Fu, Xiu-Qiong Li, Ting Guo, Hui Zhu, Pei-Li Wang, Yue Yu, Zhi-Ling Front Pharmacol Pharmacology Colorectal cancer (CRC) is a leading cause of cancer-related morbidity and mortality worldwide. Signal transducer and activator of transcription 3 (STAT3) signaling is constantly activated in CRC, and has been proposed as a pathogenic factor and a therapeutic target of CRC. Ampelopsis Radix (AR), a traditional Chinese medicinal herb, possesses low toxicity and has long been used clinically for the treatment of cancers including CRC. Some constituents of AR have been reported to exert anti-cancer properties by targeting STAT3. However, the anti-CRC mode and mechanism of action of AR have not been fully elucidated. Here, we investigated the involvement of STAT3 signaling in the anti-CRC effects of AR. Results showed that AR reduced cell viability, induced cell apoptosis, and suppressed cell migration and invasion in human HCT-116 and SW480 CRC cells. Mechanistic studies showed that AR potently suppressed STAT3 and Src phosphorylation, and inhibited STAT3 nuclear localization in cultured CRC cells. AR also downregulated the expression of STAT3 target genes Mcl-1, Bcl-xL, and MMP-2 that are involved in cell survival and mobility. Moreover, the cytotoxic effect of AR was diminished by overexpressing STAT3C, a persistent active variant of STAT3. In conclusion, AR exerted anti-CRC effects in vitro and these effects are at least in part attributed to the inhibition of STAT3 signaling. Our findings provide a molecular justification for the traditional use of AR in treating CRC, and a pharmacological basis for developing AR-derived modern anti-CRC agent(s). Frontiers Media S.A. 2017-04-28 /pmc/articles/PMC5408070/ /pubmed/28503147 http://dx.doi.org/10.3389/fphar.2017.00227 Text en Copyright © 2017 Su, Bai, Chen, Wang, Fu, Li, Guo, Zhu, Wang and Yu. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Pharmacology Su, Tao Bai, Jing-Xuan Chen, Ying-Jie Wang, Xin-Ning Fu, Xiu-Qiong Li, Ting Guo, Hui Zhu, Pei-Li Wang, Yue Yu, Zhi-Ling An Ethanolic Extract of Ampelopsis Radix Exerts Anti-colorectal Cancer Effects and Potently Inhibits STAT3 Signaling In Vitro |
title | An Ethanolic Extract of Ampelopsis Radix Exerts Anti-colorectal Cancer Effects and Potently Inhibits STAT3 Signaling In Vitro |
title_full | An Ethanolic Extract of Ampelopsis Radix Exerts Anti-colorectal Cancer Effects and Potently Inhibits STAT3 Signaling In Vitro |
title_fullStr | An Ethanolic Extract of Ampelopsis Radix Exerts Anti-colorectal Cancer Effects and Potently Inhibits STAT3 Signaling In Vitro |
title_full_unstemmed | An Ethanolic Extract of Ampelopsis Radix Exerts Anti-colorectal Cancer Effects and Potently Inhibits STAT3 Signaling In Vitro |
title_short | An Ethanolic Extract of Ampelopsis Radix Exerts Anti-colorectal Cancer Effects and Potently Inhibits STAT3 Signaling In Vitro |
title_sort | ethanolic extract of ampelopsis radix exerts anti-colorectal cancer effects and potently inhibits stat3 signaling in vitro |
topic | Pharmacology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5408070/ https://www.ncbi.nlm.nih.gov/pubmed/28503147 http://dx.doi.org/10.3389/fphar.2017.00227 |
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