Fingolimod exerts in vitro anticancer activity against hepatocellular carcinoma cell lines via YAP/TAZ suppression
Hepatocellular carcinoma (HCC) remains a notably global health challenge with high mortality rates and poor prognosis. The deregulation of the Hippo signalling pathway, especially the overexpression and activation of downstream effector Yes-associated protein (YAP), has been demonstrated to result i...
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| Format: | Article |
| Language: | English |
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Sciendo
2022-09-01
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| Series: | Acta Pharmaceutica |
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| Online Access: | https://doi.org/10.2478/acph-2022-0029 |
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| author | Du Jiamin Qian Meijia Yuan Tao Zhang Bo Chen Xueqin An Ning He Qiaojun Yang Bo Ye Song Zhu Hong |
| author_facet | Du Jiamin Qian Meijia Yuan Tao Zhang Bo Chen Xueqin An Ning He Qiaojun Yang Bo Ye Song Zhu Hong |
| author_sort | Du Jiamin |
| collection | DOAJ |
| description | Hepatocellular carcinoma (HCC) remains a notably global health challenge with high mortality rates and poor prognosis. The deregulation of the Hippo signalling pathway, especially the overexpression and activation of downstream effector Yes-associated protein (YAP), has been demonstrated to result in the rapid malignant evolution of HCC. In this context, multiple efforts have been dedicated to targeting YAP for HCC therapy, but effective YAP inhibitors are still lacking. In this study, through a YAP-TEAD (8×GTIIC) luciferase reporter assay, we identified fingolimod, an immunomodulatory drug approved for the treatment of multiple sclerosis, as a novel YAP inhibitor. Fingolimod suppressed the proliferation of HCC cell lines by downregulating the protein levels as well as the trans-activating function of YAP. Overall, our current study not only identifies fingolimod as a novel YAP-targeting in hibitor, but also indicates that this clinically-approved drug could be utilized as a potential and feasible therapeutic drug for HCC. |
| format | Article |
| id | doaj-art-233c594229f14c8a8cc91e46c3a8a926 |
| institution | Kabale University |
| issn | 1846-9558 |
| language | English |
| publishDate | 2022-09-01 |
| publisher | Sciendo |
| record_format | Article |
| series | Acta Pharmaceutica |
| spelling | doaj-art-233c594229f14c8a8cc91e46c3a8a9262025-02-02T16:18:18ZengSciendoActa Pharmaceutica1846-95582022-09-0172342743610.2478/acph-2022-0029Fingolimod exerts in vitro anticancer activity against hepatocellular carcinoma cell lines via YAP/TAZ suppressionDu Jiamin0Qian Meijia1Yuan Tao2Zhang Bo3Chen Xueqin4An Ning5He Qiaojun6Yang Bo7Ye Song8Zhu Hong9Zhejiang Province Key Laboratory of Anticancer Drug Research, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, ChinaZhejiang Province Key Laboratory of Anticancer Drug Research, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, ChinaZhejiang Province Key Laboratory of Anticancer Drug Research, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, ChinaKey Laboratory of Clinical Cancer Pharmacology and Toxicology Research of Zhejiang Province, Affiliated Hangzhou First People’s Hospital, Zhejiang University School of Medicine, Hangzhou, ChinaDepartment of Oncology, Key Laboratory of Clinical Cancer Pharmacology and Toxicology Research of Zhejiang Province, Affiliated Hangzhou First People´s Hospital, Zhejiang University School of Medicine, HangzhouChinaDepartment of Pharmacy, Ningbo Medical Center Lihuili Hospital, Ningbo, ChinaZhejiang Province Key Laboratory of Anticancer Drug Research, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, ChinaZhejiang Province Key Laboratory of Anticancer Drug Research, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, ChinaDivision of Hepatobiliary and Pancreatic Surgery, Department of Surgery, The Second Affiliated Hospital, School of Medicine Zhejiang University, Hangzhou, ChinaZhejiang Province Key Laboratory of Anticancer Drug Research, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, ChinaHepatocellular carcinoma (HCC) remains a notably global health challenge with high mortality rates and poor prognosis. The deregulation of the Hippo signalling pathway, especially the overexpression and activation of downstream effector Yes-associated protein (YAP), has been demonstrated to result in the rapid malignant evolution of HCC. In this context, multiple efforts have been dedicated to targeting YAP for HCC therapy, but effective YAP inhibitors are still lacking. In this study, through a YAP-TEAD (8×GTIIC) luciferase reporter assay, we identified fingolimod, an immunomodulatory drug approved for the treatment of multiple sclerosis, as a novel YAP inhibitor. Fingolimod suppressed the proliferation of HCC cell lines by downregulating the protein levels as well as the trans-activating function of YAP. Overall, our current study not only identifies fingolimod as a novel YAP-targeting in hibitor, but also indicates that this clinically-approved drug could be utilized as a potential and feasible therapeutic drug for HCC.https://doi.org/10.2478/acph-2022-0029fingolimodhepatocellular carcinomahippo signallingyap/taz |
| spellingShingle | Du Jiamin Qian Meijia Yuan Tao Zhang Bo Chen Xueqin An Ning He Qiaojun Yang Bo Ye Song Zhu Hong Fingolimod exerts in vitro anticancer activity against hepatocellular carcinoma cell lines via YAP/TAZ suppression Acta Pharmaceutica fingolimod hepatocellular carcinoma hippo signalling yap/taz |
| title | Fingolimod exerts in vitro anticancer activity against hepatocellular carcinoma cell lines via YAP/TAZ suppression |
| title_full | Fingolimod exerts in vitro anticancer activity against hepatocellular carcinoma cell lines via YAP/TAZ suppression |
| title_fullStr | Fingolimod exerts in vitro anticancer activity against hepatocellular carcinoma cell lines via YAP/TAZ suppression |
| title_full_unstemmed | Fingolimod exerts in vitro anticancer activity against hepatocellular carcinoma cell lines via YAP/TAZ suppression |
| title_short | Fingolimod exerts in vitro anticancer activity against hepatocellular carcinoma cell lines via YAP/TAZ suppression |
| title_sort | fingolimod exerts in vitro anticancer activity against hepatocellular carcinoma cell lines via yap taz suppression |
| topic | fingolimod hepatocellular carcinoma hippo signalling yap/taz |
| url | https://doi.org/10.2478/acph-2022-0029 |
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