Abstract:
:Differences in the metabolism of cancer cells or cancer stem cells (CSCs) as compared to normal cells have provided avenues to safely target cancers. To discover metabolic inhibitors of CSCs, we performed alkaline phosphatase- and tumoursphere-based drug screening using induced cancer stem cell-like cells. From the screening of a RIKEN NPDepo chemical library, we discovered NPD2381 as a novel and selective cancer-stemness inhibitor that targets mitochondrial metabolism. Using our ChemProteoBase profiling, we found that NPD2381 increases the expression of enzymes within the serine biosynthesis pathway. We also found a role for serine in protecting cancer cells from mitochondrial inhibitors. Our results suggest the existence of a compensatory mechanism to increase the level of intracellular serine in response to mitochondrial inhibitors.
journal_name
FEBS Lettjournal_title
FEBS lettersauthors
Subedi A,Muroi M,Futamura Y,Kawamura T,Aono H,Nishi M,Ryo A,Watanabe N,Osada Hdoi
10.1002/1873-3468.13361subject
Has Abstractpub_date
2019-04-01 00:00:00pages
763-776issue
8eissn
0014-5793issn
1873-3468journal_volume
593pub_type
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