Products Cited in Publications Worldwide Isorhapontigenin protects against doxorubicin-induced cardiotoxicity via increasing YAP1 expression

Isorhapontigenin protects against doxorubicin-induced cardiotoxicity via increasing YAP1 expression

Wang, Panxia; Wang, Minghui; Hu, Yuehuai; Chen, Jianxing; Cao, Yanjun; Liu, Cui; Wu, Zhongkai; Shen, Juan; Lu, Jing; Liu, Peiqing

DOI: PMID:

Abstract

As an effective anticancer drug, the clinical limitation of doxorubicin (Dox) is the time- and dose-dependent cardiotoxicity. Yes-associated protein 1 (YAP1) interacts with transcription factor TEA domain 1 (TEAD1) and plays an important role in cell proliferation and survival. However, the role of YAP1 in Dox-induced cardiomyopathy has not been reported. In this study, the expression of YAP1 was reduced in clinical human failing hearts with dilated cardiomyopathy and Dox-induced in vivo and in vitro cardiotoxic model. Ectopic expression of Yap1 significantly blocked Dox-induced cardiomyocytes apoptosis in TEAD1 dependent manner. Isorhapontigenin (Isor) is a new derivative of stilbene and responsible for a wide range of biological processes. Here, we found that Isor effectively relieved Dox-induced cardiomyocytes apoptosis in a dose-dependent manner in vitro. Administration with Isor (30 mg/kg/day, intraperitoneally, 3 weeks) significantly protected against Dox-induced cardiotoxicity in mice. Interestingly, Isor increased Dox-caused repression in YAP1 and the expression of its target genes in vivo and in vitro. Knockout or inhibition of Yap1 blocked the protective effects of Isor on Dox-induced cardiotoxicity. In conclusion, YAP1 may be a novel target for Dox-induced cardiotoxicity and Isor might be a new compound to fight against Dox-induced cardiotoxicity by increasing YAP1 expression.

Keywords

Isorhapontigenin ; YAP1 ; Doxorubicin ; Cardiotoxicity ; Cardiomyocytes apoptosis ; TEAD1 ; Connective tissue growth factor ; Amphiregulin

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Isorhapontigenin

A53172932507-66-795%

Isorhapontigenin

11.0/1mg

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