The Disulfiram/Copper Complex Induces Autophagic Cell Death in Colorectal Cancer by Targeting ULK1

Colorectal cancer (CRC) is highly prevalent worldwide, but there has been limited development of efficient and affordable treatment. Induced autophagy has recently been recognized as a novel therapeutic strategy in cancer treatment, and disulfiram (DSF), a well-known antialcohol drug, is also found...

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Autores principales:	Yeting Hu, Yucheng Qian, Jingsun Wei, Tian Jin, Xiangxing Kong, Hongfeng Cao, Kefeng Ding
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	disulfiram autophagy ULK1 CRISPR library colorectal cancer Therapeutics. Pharmacology RM1-950
Acceso en línea:	https://doaj.org/article/3e21a7c15e524d1b9d505466fa34c89f
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spelling	oai:doaj.org-article:3e21a7c15e524d1b9d505466fa34c89f2021-11-30T12:46:44ZThe Disulfiram/Copper Complex Induces Autophagic Cell Death in Colorectal Cancer by Targeting ULK11663-981210.3389/fphar.2021.752825https://doaj.org/article/3e21a7c15e524d1b9d505466fa34c89f2021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fphar.2021.752825/fullhttps://doaj.org/toc/1663-9812Colorectal cancer (CRC) is highly prevalent worldwide, but there has been limited development of efficient and affordable treatment. Induced autophagy has recently been recognized as a novel therapeutic strategy in cancer treatment, and disulfiram (DSF), a well-known antialcohol drug, is also found to inhibit tumor growth in various malignancies. Recently, DSF has been reported to induce excessive autophagy in oral squamous cells; however, little is known about whether it can induce autophagy and suppress proliferation in CRC. In this study, we investigate the effect of DSF with copper (DSF/Cu) on CRC both in vitro and in vivo and find that the combination significantly inhibits CRC cell viability and mainly induces autophagy instead of apoptosis. Furthermore, we use whole genome CRISPR library screening and identify a new mechanism by which DSF triggers autophagy by ULK1. Overall, these findings provide a potential CRC treatment.Yeting HuYucheng QianJingsun WeiTian JinXiangxing KongHongfeng CaoKefeng DingKefeng DingFrontiers Media S.A.articledisulfiramautophagyULK1CRISPR librarycolorectal cancerTherapeutics. PharmacologyRM1-950ENFrontiers in Pharmacology, Vol 12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	disulfiram autophagy ULK1 CRISPR library colorectal cancer Therapeutics. Pharmacology RM1-950
spellingShingle	disulfiram autophagy ULK1 CRISPR library colorectal cancer Therapeutics. Pharmacology RM1-950 Yeting Hu Yucheng Qian Jingsun Wei Tian Jin Xiangxing Kong Hongfeng Cao Kefeng Ding Kefeng Ding The Disulfiram/Copper Complex Induces Autophagic Cell Death in Colorectal Cancer by Targeting ULK1
description	Colorectal cancer (CRC) is highly prevalent worldwide, but there has been limited development of efficient and affordable treatment. Induced autophagy has recently been recognized as a novel therapeutic strategy in cancer treatment, and disulfiram (DSF), a well-known antialcohol drug, is also found to inhibit tumor growth in various malignancies. Recently, DSF has been reported to induce excessive autophagy in oral squamous cells; however, little is known about whether it can induce autophagy and suppress proliferation in CRC. In this study, we investigate the effect of DSF with copper (DSF/Cu) on CRC both in vitro and in vivo and find that the combination significantly inhibits CRC cell viability and mainly induces autophagy instead of apoptosis. Furthermore, we use whole genome CRISPR library screening and identify a new mechanism by which DSF triggers autophagy by ULK1. Overall, these findings provide a potential CRC treatment.
format	article
author	Yeting Hu Yucheng Qian Jingsun Wei Tian Jin Xiangxing Kong Hongfeng Cao Kefeng Ding Kefeng Ding
author_facet	Yeting Hu Yucheng Qian Jingsun Wei Tian Jin Xiangxing Kong Hongfeng Cao Kefeng Ding Kefeng Ding
author_sort	Yeting Hu
title	The Disulfiram/Copper Complex Induces Autophagic Cell Death in Colorectal Cancer by Targeting ULK1
title_short	The Disulfiram/Copper Complex Induces Autophagic Cell Death in Colorectal Cancer by Targeting ULK1
title_full	The Disulfiram/Copper Complex Induces Autophagic Cell Death in Colorectal Cancer by Targeting ULK1
title_fullStr	The Disulfiram/Copper Complex Induces Autophagic Cell Death in Colorectal Cancer by Targeting ULK1
title_full_unstemmed	The Disulfiram/Copper Complex Induces Autophagic Cell Death in Colorectal Cancer by Targeting ULK1
title_sort	disulfiram/copper complex induces autophagic cell death in colorectal cancer by targeting ulk1
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/3e21a7c15e524d1b9d505466fa34c89f
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The Disulfiram/Copper Complex Induces Autophagic Cell Death in Colorectal Cancer by Targeting ULK1

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