期刊
FRONTIERS IN PHARMACOLOGY
卷 12, 期 -, 页码 -出版社
FRONTIERS MEDIA SA
DOI: 10.3389/fphar.2021.752825
关键词
disulfiram; autophagy; ULK1; CRISPR library; colorectal cancer
资金
- National Natural Science Foundation of China [81802750, 81772545, 82072624]
- Key Technology Research and Development Program of Zhejiang Province
This study explores the therapeutic effect of DSF with copper on CRC, showing that the combination significantly inhibits CRC cell viability by inducing autophagy instead of apoptosis. Furthermore, a new mechanism by which DSF triggers autophagy through ULK1 is identified using whole genome CRISPR library screening.
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.
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