Emodin succinyl ester inhibits malignant proliferation and migration of hepatocellular carcinoma by suppressing the interaction of AR and EZH2 - 18/06/20
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Graphical abstract |
Highlights |
• | Emodin derivative ESE effectively inhibits HCC cell proliferation and migration. |
• | AR/EZH2 signaling is the key target for ESE to suppress HCC cell growth and migration. |
• | ESE shows a potent role in suppressing HCC tumorigenesis in vivo models. |
• | ESE is a promising anti-tumor candidate without toxicity on hepatorenal function. |
Abstract |
Emodin is a promising anti-cancer reagent. To improve the physicochemical and anti-cancer property, we modified its structure and get a derivative called emodin succinyl ester (ESE). Here, we investigated the effect of ESE on the suppression of hepatocellular carcinoma (HCC) and the underlying mechanism. Our results showed that ESE strongly inhibited HCC cell proliferation and migration in vitro. Further study revealed that ESE treatment decreased transcription level and protein expression of androgen receptor (AR) and enhancer of zeste homolog 2 (EZH2), two key factors interacting to promote aggressive HCC development. Conversely, overexpression of AR attenuated the inhibitory effect of ESE on EZH2 expression, and vice versa. Importantly, overexpression of AR or EZH2 could counteract ESE-suppressed cell proliferation and migration. The association of ESE-targeted AR and EZH2 with the suppression of tumorigenicity was further confirmed in xenograft and diethylnitrosamine (DEN)-induced HCC mouse models. These findings validate the therapeutic effect of ESE on HCC aggression by targeting the interaction of AR and EZH2, suggesting ESE may be a potent drug in the clinical treatment of HCC.
El texto completo de este artículo está disponible en PDF.Keywords : Emodin succinyl ester, Hepatocellular carcinoma, Androgen receptor, Enhancer of zeste homolog 2
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Vol 128
Artículo 110244- août 2020 Regresar al númeroBienvenido a EM-consulte, la referencia de los profesionales de la salud.
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