Isoliquiritigenin Reverses Epithelial-Mesenchymal Transition Through Modulation of the TGF-β/Smad Signaling Pathway in Endometrial Cancer
Endometrial cancer is a common gynecological cancer with a poor prognosis, mostly attributed to tumor metastasis. Epithelial–mesenchymal transition (EMT) can be mediated via transforming growth factor beta (TGF-β) signaling pathway, facilitating the ability of cancer cell invasion and migration. Iso...
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MDPI AG
2021-03-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/13/6/1236 |
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| author | Hsin-Yuan Chen Yi-Fen Chiang Jia-Syuan Huang Tsui-Chin Huang Yin-Hwa Shih Kai-Lee Wang Mohamed Ali Yong-Han Hong Tzong-Ming Shieh Shih-Min Hsia |
| author_facet | Hsin-Yuan Chen Yi-Fen Chiang Jia-Syuan Huang Tsui-Chin Huang Yin-Hwa Shih Kai-Lee Wang Mohamed Ali Yong-Han Hong Tzong-Ming Shieh Shih-Min Hsia |
| author_sort | Hsin-Yuan Chen |
| collection | DOAJ |
| description | Endometrial cancer is a common gynecological cancer with a poor prognosis, mostly attributed to tumor metastasis. Epithelial–mesenchymal transition (EMT) can be mediated via transforming growth factor beta (TGF-β) signaling pathway, facilitating the ability of cancer cell invasion and migration. Isoliquiritigenin (ISL) is a flavonoid derived from licorice with reported antineoplastic activities. This study aims to investigate the anti-metastatic potential of ISL on endometrial cancer both in vitro and in vivo. First, human endometrial cancer cell lines (HEC-1A, Ishikawa, and RL95-2) were treated with ISL and then subjected to functional assays such as migration assay as well as molecular analyses including immunoblotting, immunofluorescence and RT-qPCR. In addition, HEC-1A-LUC cells were implanted into female nude mice and treated with ISL by intraperitoneal injection for four weeks. Results showed that ISL inhibited cell migration and reversed the effect of TGF-β on the expression of E-cadherin, N-cadherin, vimentin, α-SMA, p-Smad3, and TWIST1/2 In vitro. Interestingly, In vivo study revealed that ISL reduced peritoneal dissemination and serum level of TGF-β1, as well as decreased the expression levels of N-cadherin, p-Smad2/3, TWIST1/2, while increased E-cadherin. Overall, ISL reverses the EMT through targeting the TGF-β/Smad signaling pathway and features a potential therapeutic treatment for metastatic endometrial cancer. |
| first_indexed | 2024-03-10T13:19:45Z |
| format | Article |
| id | doaj.art-dc764b7ece7341a6a5f819a357440f32 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-10T13:19:45Z |
| publishDate | 2021-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-dc764b7ece7341a6a5f819a357440f322023-11-21T10:07:24ZengMDPI AGCancers2072-66942021-03-01136123610.3390/cancers13061236Isoliquiritigenin Reverses Epithelial-Mesenchymal Transition Through Modulation of the TGF-β/Smad Signaling Pathway in Endometrial CancerHsin-Yuan Chen0Yi-Fen Chiang1Jia-Syuan Huang2Tsui-Chin Huang3Yin-Hwa Shih4Kai-Lee Wang5Mohamed Ali6Yong-Han Hong7Tzong-Ming Shieh8Shih-Min Hsia9School of Nutrition and Health Sciences, College of Nutrition, Taipei Medical University, Taipei 11031, TaiwanSchool of Nutrition and Health Sciences, College of Nutrition, Taipei Medical University, Taipei 11031, TaiwanSchool of Nutrition and Health Sciences, College of Nutrition, Taipei Medical University, Taipei 11031, TaiwanGraduate Institute of Cancer Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei 11031, TaiwanDepartment of Healthcare Administration, Asia University, Taichung 41354, TaiwanDepartment of Nursing, Ching Kuo Institute of Management and Health, Keelung 20301, TaiwanClinical Pharmacy Department, Faculty of Pharmacy, Ain Shams University, Cairo 11566, EgyptDepartment of Nutrition, I-Shou University, Kaohsiung 84001, TaiwanSchool of Dentistry, College of Dentistry, China Medical University, Taichung 40402, TaiwanSchool of Nutrition and Health Sciences, College of Nutrition, Taipei Medical University, Taipei 11031, TaiwanEndometrial cancer is a common gynecological cancer with a poor prognosis, mostly attributed to tumor metastasis. Epithelial–mesenchymal transition (EMT) can be mediated via transforming growth factor beta (TGF-β) signaling pathway, facilitating the ability of cancer cell invasion and migration. Isoliquiritigenin (ISL) is a flavonoid derived from licorice with reported antineoplastic activities. This study aims to investigate the anti-metastatic potential of ISL on endometrial cancer both in vitro and in vivo. First, human endometrial cancer cell lines (HEC-1A, Ishikawa, and RL95-2) were treated with ISL and then subjected to functional assays such as migration assay as well as molecular analyses including immunoblotting, immunofluorescence and RT-qPCR. In addition, HEC-1A-LUC cells were implanted into female nude mice and treated with ISL by intraperitoneal injection for four weeks. Results showed that ISL inhibited cell migration and reversed the effect of TGF-β on the expression of E-cadherin, N-cadherin, vimentin, α-SMA, p-Smad3, and TWIST1/2 In vitro. Interestingly, In vivo study revealed that ISL reduced peritoneal dissemination and serum level of TGF-β1, as well as decreased the expression levels of N-cadherin, p-Smad2/3, TWIST1/2, while increased E-cadherin. Overall, ISL reverses the EMT through targeting the TGF-β/Smad signaling pathway and features a potential therapeutic treatment for metastatic endometrial cancer.https://www.mdpi.com/2072-6694/13/6/1236endometrial cancerisoliquiritigeninepithelial–mesenchymal transitiontransforming growth factor betametastasis |
| spellingShingle | Hsin-Yuan Chen Yi-Fen Chiang Jia-Syuan Huang Tsui-Chin Huang Yin-Hwa Shih Kai-Lee Wang Mohamed Ali Yong-Han Hong Tzong-Ming Shieh Shih-Min Hsia Isoliquiritigenin Reverses Epithelial-Mesenchymal Transition Through Modulation of the TGF-β/Smad Signaling Pathway in Endometrial Cancer Cancers endometrial cancer isoliquiritigenin epithelial–mesenchymal transition transforming growth factor beta metastasis |
| title | Isoliquiritigenin Reverses Epithelial-Mesenchymal Transition Through Modulation of the TGF-β/Smad Signaling Pathway in Endometrial Cancer |
| title_full | Isoliquiritigenin Reverses Epithelial-Mesenchymal Transition Through Modulation of the TGF-β/Smad Signaling Pathway in Endometrial Cancer |
| title_fullStr | Isoliquiritigenin Reverses Epithelial-Mesenchymal Transition Through Modulation of the TGF-β/Smad Signaling Pathway in Endometrial Cancer |
| title_full_unstemmed | Isoliquiritigenin Reverses Epithelial-Mesenchymal Transition Through Modulation of the TGF-β/Smad Signaling Pathway in Endometrial Cancer |
| title_short | Isoliquiritigenin Reverses Epithelial-Mesenchymal Transition Through Modulation of the TGF-β/Smad Signaling Pathway in Endometrial Cancer |
| title_sort | isoliquiritigenin reverses epithelial mesenchymal transition through modulation of the tgf β smad signaling pathway in endometrial cancer |
| topic | endometrial cancer isoliquiritigenin epithelial–mesenchymal transition transforming growth factor beta metastasis |
| url | https://www.mdpi.com/2072-6694/13/6/1236 |
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