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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Main Authors: Yeting Hu (Author), Yucheng Qian (Author), Jingsun Wei (Author), Tian Jin (Author), Xiangxing Kong (Author), Hongfeng Cao (Author), Kefeng Ding (Author)
Format: Book
Published: Frontiers Media S.A., 2021-11-01T00:00:00Z.
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100 1 0 |a Yeting Hu  |e author 
700 1 0 |a Yucheng Qian  |e author 
700 1 0 |a Jingsun Wei  |e author 
700 1 0 |a Tian Jin  |e author 
700 1 0 |a Xiangxing Kong  |e author 
700 1 0 |a Hongfeng Cao  |e author 
700 1 0 |a Kefeng Ding  |e author 
700 1 0 |a Kefeng Ding  |e author 
245 0 0 |a The Disulfiram/Copper Complex Induces Autophagic Cell Death in Colorectal Cancer by Targeting ULK1 
260 |b Frontiers Media S.A.,   |c 2021-11-01T00:00:00Z. 
500 |a 1663-9812 
500 |a 10.3389/fphar.2021.752825 
520 |a 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. 
546 |a EN 
690 |a disulfiram 
690 |a autophagy 
690 |a ULK1 
690 |a CRISPR library 
690 |a colorectal cancer 
690 |a Therapeutics. Pharmacology 
690 |a RM1-950 
655 7 |a article  |2 local 
786 0 |n Frontiers in Pharmacology, Vol 12 (2021) 
787 0 |n https://www.frontiersin.org/articles/10.3389/fphar.2021.752825/full 
787 0 |n https://doaj.org/toc/1663-9812 
856 4 1 |u https://doaj.org/article/3e21a7c15e524d1b9d505466fa34c89f  |z Connect to this object online.