Bruceine D inhibits HIF-1α-mediated glucose metabolism in hepatocellular carcinoma by blocking ICAT/β-catenin interaction

Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related deaths, characterized by highly hypoxic tumor microenvironment. Hypoxia-inducible factor-1α (HIF-1α) is a major regulator involved in cellular response to changes of oxygen levels, supporting the adaptation of tumor cells...

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Autores principales:	Rui Huang, Lijun Zhang, Jinmei Jin, Yudong Zhou, Hongwei Zhang, Chao Lv, Dong Lu, Ye Wu, Hong Zhang, Sanhong Liu, Hongzhuan Chen, Xin Luan, Weidong Zhang
Formato:	article
Lenguaje:	EN
Publicado:	Elsevier 2021
Materias:	Hepatocellular carcinoma Bruceine D HIF-1α Metabolism ICAT β-Catenin Therapeutics. Pharmacology RM1-950
Acceso en línea:	https://doaj.org/article/65ee77163efc470faa04d607d8d745fa
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spelling	oai:doaj.org-article:65ee77163efc470faa04d607d8d745fa2021-12-02T05:01:24ZBruceine D inhibits HIF-1α-mediated glucose metabolism in hepatocellular carcinoma by blocking ICAT/β-catenin interaction2211-383510.1016/j.apsb.2021.05.009https://doaj.org/article/65ee77163efc470faa04d607d8d745fa2021-11-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S2211383521001751https://doaj.org/toc/2211-3835Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related deaths, characterized by highly hypoxic tumor microenvironment. Hypoxia-inducible factor-1α (HIF-1α) is a major regulator involved in cellular response to changes of oxygen levels, supporting the adaptation of tumor cells to hypoxia. Bruceine D (BD) is an isolated natural quassinoid with multiple anti-cancer effects. Here, we identified BD could significantly inhibit the HIF-1α expression and its subsequently mediated HCC cell metabolism. Using biophysical proteomics approaches, we identified inhibitor of β-catenin and T-cell factor (ICAT) as the functional target of BD. By targeting ICAT, BD disrupted the interaction of β-catenin and ICAT, and promoted β-catenin degradation, which in turn induced the decrease of HIF-1α expression. Furthermore, BD could inhibit HCC cells proliferation and tumor growth in vivo, and knockdown of ICAT substantially increased resistance to BD treatment in vitro. Our data highlight the potential of BD as a modulator of β-catenin/HIF-1α axis mediated HCC metabolism.Rui HuangLijun ZhangJinmei JinYudong ZhouHongwei ZhangChao LvDong LuYe WuHong ZhangSanhong LiuHongzhuan ChenXin LuanWeidong ZhangElsevierarticleHepatocellular carcinomaBruceine DHIF-1αMetabolismICATβ-CateninTherapeutics. PharmacologyRM1-950ENActa Pharmaceutica Sinica B, Vol 11, Iss 11, Pp 3481-3492 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Hepatocellular carcinoma Bruceine D HIF-1α Metabolism ICAT β-Catenin Therapeutics. Pharmacology RM1-950
spellingShingle	Hepatocellular carcinoma Bruceine D HIF-1α Metabolism ICAT β-Catenin Therapeutics. Pharmacology RM1-950 Rui Huang Lijun Zhang Jinmei Jin Yudong Zhou Hongwei Zhang Chao Lv Dong Lu Ye Wu Hong Zhang Sanhong Liu Hongzhuan Chen Xin Luan Weidong Zhang Bruceine D inhibits HIF-1α-mediated glucose metabolism in hepatocellular carcinoma by blocking ICAT/β-catenin interaction
description	Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related deaths, characterized by highly hypoxic tumor microenvironment. Hypoxia-inducible factor-1α (HIF-1α) is a major regulator involved in cellular response to changes of oxygen levels, supporting the adaptation of tumor cells to hypoxia. Bruceine D (BD) is an isolated natural quassinoid with multiple anti-cancer effects. Here, we identified BD could significantly inhibit the HIF-1α expression and its subsequently mediated HCC cell metabolism. Using biophysical proteomics approaches, we identified inhibitor of β-catenin and T-cell factor (ICAT) as the functional target of BD. By targeting ICAT, BD disrupted the interaction of β-catenin and ICAT, and promoted β-catenin degradation, which in turn induced the decrease of HIF-1α expression. Furthermore, BD could inhibit HCC cells proliferation and tumor growth in vivo, and knockdown of ICAT substantially increased resistance to BD treatment in vitro. Our data highlight the potential of BD as a modulator of β-catenin/HIF-1α axis mediated HCC metabolism.
format	article
author	Rui Huang Lijun Zhang Jinmei Jin Yudong Zhou Hongwei Zhang Chao Lv Dong Lu Ye Wu Hong Zhang Sanhong Liu Hongzhuan Chen Xin Luan Weidong Zhang
author_facet	Rui Huang Lijun Zhang Jinmei Jin Yudong Zhou Hongwei Zhang Chao Lv Dong Lu Ye Wu Hong Zhang Sanhong Liu Hongzhuan Chen Xin Luan Weidong Zhang
author_sort	Rui Huang
title	Bruceine D inhibits HIF-1α-mediated glucose metabolism in hepatocellular carcinoma by blocking ICAT/β-catenin interaction
title_short	Bruceine D inhibits HIF-1α-mediated glucose metabolism in hepatocellular carcinoma by blocking ICAT/β-catenin interaction
title_full	Bruceine D inhibits HIF-1α-mediated glucose metabolism in hepatocellular carcinoma by blocking ICAT/β-catenin interaction
title_fullStr	Bruceine D inhibits HIF-1α-mediated glucose metabolism in hepatocellular carcinoma by blocking ICAT/β-catenin interaction
title_full_unstemmed	Bruceine D inhibits HIF-1α-mediated glucose metabolism in hepatocellular carcinoma by blocking ICAT/β-catenin interaction
title_sort	bruceine d inhibits hif-1α-mediated glucose metabolism in hepatocellular carcinoma by blocking icat/β-catenin interaction
publisher	Elsevier
publishDate	2021
url	https://doaj.org/article/65ee77163efc470faa04d607d8d745fa
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Bruceine D inhibits HIF-1α-mediated glucose metabolism in hepatocellular carcinoma by blocking ICAT/β-catenin interaction

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