A novel inhibitor of tumorspheres reveals the activation of the serine biosynthetic pathway upon mitochondrial inhibition.
FEBS Lett
; 593(8): 763-776, 2019 04.
Article
in En
| MEDLINE
| ID: mdl-30874300
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.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Serine
/
Mitochondria
/
Antineoplastic Agents
Limits:
Humans
Language:
En
Journal:
FEBS Lett
Year:
2019
Document type:
Article
Affiliation country: