Tanshinone IIA Inhibits Epithelial-to-Mesenchymal Transition Through Hindering β-Arrestin1 Mediated β-Catenin Signaling Pathway in Colorectal Cancer
Tanshinone IIA (Tan IIA) is a major active ingredient extracted from Salvia miltiorrhiza, which has been proved to be able to inhibit metastasis of various cancers including colorectal cancer (CRC). However, the mechanisms of anti-metastatic effect of Tan IIA on CRC are not well explored. A number o...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2020-10-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2020.586616/full |
| _version_ | 1818549580123340800 |
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| author | Qing Song Qing Song Qing Song Liu Yang Liu Yang Liu Yang Zhifen Han Zhifen Han Xinnan Wu Xinnan Wu Ruixiao Li Ruixiao Li Lihong Zhou Lihong Zhou Ningning Liu Ningning Liu Hua Sui Hua Sui Jianfeng Cai Yan Wang Yan Wang Qing Ji Qing Ji Qi Li Qi Li |
| author_facet | Qing Song Qing Song Qing Song Liu Yang Liu Yang Liu Yang Zhifen Han Zhifen Han Xinnan Wu Xinnan Wu Ruixiao Li Ruixiao Li Lihong Zhou Lihong Zhou Ningning Liu Ningning Liu Hua Sui Hua Sui Jianfeng Cai Yan Wang Yan Wang Qing Ji Qing Ji Qi Li Qi Li |
| author_sort | Qing Song |
| collection | DOAJ |
| description | Tanshinone IIA (Tan IIA) is a major active ingredient extracted from Salvia miltiorrhiza, which has been proved to be able to inhibit metastasis of various cancers including colorectal cancer (CRC). However, the mechanisms of anti-metastatic effect of Tan IIA on CRC are not well explored. A number of studies indicate that epithelial-to-mesenchymal transition (EMT) plays an important role in CRC metastasis, and our previous studies demonstrate that β-arrestin1could regulate EMT in CRC partly through β-catenin signaling pathway. In this work, we investigate whether Tan IIA could regulate EMT in CRC through β-arrestin1-mediated β-catenin signaling pathway both in vivo and in vitro. Our results showed that Tan IIA inhibited lung metastases of CRC cells in vivo and extended the survival time of mice with CRC. In vitro, Tan IIA increased the expression of E-cadherin, decreased the expression of Snail, N-cadherin and Vimentin, thus suppressed EMT and the migratory ability of CRC cells. Further study found that the mechanism of action of Tan IIA in regulating EMT and metastasis is associated with the suppression of β-arrestin1 expression, resulting in the increase of GSK-3β expression, reduction of β-catenin nuclear localization, thereby decreased the activity of β-catenin signaling pathway. Our data revealed a new mechanism of Tan IIA on the suppression of EMT and metastasis in CRC via β-arrestin1-mediated β-catenin signaling pathway and provided support for using Tan IIA as anti-metastatic agents in CRC. |
| first_indexed | 2024-12-12T08:35:12Z |
| format | Article |
| id | doaj.art-76254a3691fd4b4989682cc03ad1d627 |
| institution | Directory Open Access Journal |
| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-12-12T08:35:12Z |
| publishDate | 2020-10-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj.art-76254a3691fd4b4989682cc03ad1d6272022-12-22T00:30:57ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122020-10-011110.3389/fphar.2020.586616586616Tanshinone IIA Inhibits Epithelial-to-Mesenchymal Transition Through Hindering β-Arrestin1 Mediated β-Catenin Signaling Pathway in Colorectal CancerQing Song0Qing Song1Qing Song2Liu Yang3Liu Yang4Liu Yang5Zhifen Han6Zhifen Han7Xinnan Wu8Xinnan Wu9Ruixiao Li10Ruixiao Li11Lihong Zhou12Lihong Zhou13Ningning Liu14Ningning Liu15Hua Sui16Hua Sui17Jianfeng Cai18Yan Wang19Yan Wang20Qing Ji21Qing Ji22Qi Li23Qi Li24Department of Medical Oncology and Cancer Institute of Integrative Medicine, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaAcademy of Integrative Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaDepartment of Medical Oncology, Suzhou TCM Hospital Affiliated to Nanjing University of Chinese Medicine, Suzhou, ChinaDepartment of Medical Oncology and Cancer Institute of Integrative Medicine, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaAcademy of Integrative Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaDepartment of Oncology, Baoshan Branch, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaDepartment of Medical Oncology and Cancer Institute of Integrative Medicine, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaAcademy of Integrative Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaDepartment of Medical Oncology and Cancer Institute of Integrative Medicine, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaAcademy of Integrative Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaDepartment of Medical Oncology and Cancer Institute of Integrative Medicine, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaAcademy of Integrative Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaDepartment of Medical Oncology and Cancer Institute of Integrative Medicine, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaAcademy of Integrative Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaDepartment of Medical Oncology and Cancer Institute of Integrative Medicine, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaAcademy of Integrative Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaDepartment of Medical Oncology and Cancer Institute of Integrative Medicine, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaAcademy of Integrative Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaDepartment of Chemistry, University of South Florida, Tampa, FL, United StatesDepartment of Medical Oncology and Cancer Institute of Integrative Medicine, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaAcademy of Integrative Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaDepartment of Medical Oncology and Cancer Institute of Integrative Medicine, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaAcademy of Integrative Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaDepartment of Medical Oncology and Cancer Institute of Integrative Medicine, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaAcademy of Integrative Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaTanshinone IIA (Tan IIA) is a major active ingredient extracted from Salvia miltiorrhiza, which has been proved to be able to inhibit metastasis of various cancers including colorectal cancer (CRC). However, the mechanisms of anti-metastatic effect of Tan IIA on CRC are not well explored. A number of studies indicate that epithelial-to-mesenchymal transition (EMT) plays an important role in CRC metastasis, and our previous studies demonstrate that β-arrestin1could regulate EMT in CRC partly through β-catenin signaling pathway. In this work, we investigate whether Tan IIA could regulate EMT in CRC through β-arrestin1-mediated β-catenin signaling pathway both in vivo and in vitro. Our results showed that Tan IIA inhibited lung metastases of CRC cells in vivo and extended the survival time of mice with CRC. In vitro, Tan IIA increased the expression of E-cadherin, decreased the expression of Snail, N-cadherin and Vimentin, thus suppressed EMT and the migratory ability of CRC cells. Further study found that the mechanism of action of Tan IIA in regulating EMT and metastasis is associated with the suppression of β-arrestin1 expression, resulting in the increase of GSK-3β expression, reduction of β-catenin nuclear localization, thereby decreased the activity of β-catenin signaling pathway. Our data revealed a new mechanism of Tan IIA on the suppression of EMT and metastasis in CRC via β-arrestin1-mediated β-catenin signaling pathway and provided support for using Tan IIA as anti-metastatic agents in CRC.https://www.frontiersin.org/articles/10.3389/fphar.2020.586616/fulltanshinone IIAcolorectal cancerepithelial-to-mesenchymal transitionβ-arrestin1β-catenin signaling pathway |
| spellingShingle | Qing Song Qing Song Qing Song Liu Yang Liu Yang Liu Yang Zhifen Han Zhifen Han Xinnan Wu Xinnan Wu Ruixiao Li Ruixiao Li Lihong Zhou Lihong Zhou Ningning Liu Ningning Liu Hua Sui Hua Sui Jianfeng Cai Yan Wang Yan Wang Qing Ji Qing Ji Qi Li Qi Li Tanshinone IIA Inhibits Epithelial-to-Mesenchymal Transition Through Hindering β-Arrestin1 Mediated β-Catenin Signaling Pathway in Colorectal Cancer Frontiers in Pharmacology tanshinone IIA colorectal cancer epithelial-to-mesenchymal transition β-arrestin1 β-catenin signaling pathway |
| title | Tanshinone IIA Inhibits Epithelial-to-Mesenchymal Transition Through Hindering β-Arrestin1 Mediated β-Catenin Signaling Pathway in Colorectal Cancer |
| title_full | Tanshinone IIA Inhibits Epithelial-to-Mesenchymal Transition Through Hindering β-Arrestin1 Mediated β-Catenin Signaling Pathway in Colorectal Cancer |
| title_fullStr | Tanshinone IIA Inhibits Epithelial-to-Mesenchymal Transition Through Hindering β-Arrestin1 Mediated β-Catenin Signaling Pathway in Colorectal Cancer |
| title_full_unstemmed | Tanshinone IIA Inhibits Epithelial-to-Mesenchymal Transition Through Hindering β-Arrestin1 Mediated β-Catenin Signaling Pathway in Colorectal Cancer |
| title_short | Tanshinone IIA Inhibits Epithelial-to-Mesenchymal Transition Through Hindering β-Arrestin1 Mediated β-Catenin Signaling Pathway in Colorectal Cancer |
| title_sort | tanshinone iia inhibits epithelial to mesenchymal transition through hindering β arrestin1 mediated β catenin signaling pathway in colorectal cancer |
| topic | tanshinone IIA colorectal cancer epithelial-to-mesenchymal transition β-arrestin1 β-catenin signaling pathway |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2020.586616/full |
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