Original scientific paper

https://doi.org/10.2478/acph-2022-0029

Fingolimod exerts in vitro anticancer activity against hepatocellular carcinoma cell lines via YAP/TAZ suppression

JIAMIN DU ; Zhejiang Province Key Laboratory of Anti-Cancer Drug Research, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, China
MEIJIA QIAN ; Zhejiang Province Key Laboratory of Anti-Cancer Drug Research, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, China
TAO YUAN ; Zhejiang Province Key Laboratory of Anti-Cancer Drug Research, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, China
BO ZHANG ; Key Laboratory of Clinical Cancer Pharmacology and Toxicology Research of Zhejiang Province, Affiliated Hangzhou First People’s Hospital, Zhejiang University School of Medicine, Hangzhou, China
XUEQIN CHEN ; 3 Department 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, Hangzhou, China
NING AN ; Department of Pharmacy, Ningbo Medical Center Lihuili Hospital, Ningbo, China
QIAOJUN HE ; Zhejiang Province Key Laboratory of Anti-Cancer Drug Research, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, China
BO YANG ; Zhejiang Province Key Laboratory of Anti-Cancer Drug Research, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, China
SONG YE ; Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
HONG ZHU ; Zhejiang Province Key Laboratory of Anti-Cancer Drug Research, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, China; Key Laboratory of Clinical Cancer Pharmacology and Toxicology Research of Zhejiang Province, Affiliated Hangzhou First People’s Hospital, Zhejiang University School of Medicine, Hangzhou, China; The Westlake Laboratory of Life Sciences and Biomedicine, Hangzhou, China

Abstract

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 transactivating function of YAP. Overall, our current study not only identifies fingolimod as a novel YAP-targeting inhibitor, but also indicates that this clinically-approved drug could be utilized as a potential and feasible therapeutic drug for HCC.

Keywords

fingolimod; hepatocellular carcinoma; hippo signaling; YAP/TAZ

Hrčak ID:

271294

URI

https://hrcak.srce.hr/271294

Publication date:

30.9.2022.

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