Profiling of Nutrient Transporter Expression in Human Stem Cell-Derived Cardiomyocytes Exposed to Tyrosine Kinase Inhibitor Anticancer Drugs Using RBD Ligands.
J Biomol Screen
; 19(8): 1185-92, 2014 Sep.
Article
in En
| MEDLINE
| ID: mdl-24809354
We applied a novel profiling approach using receptor binding domain (RBD) ligands to cell surface domains of a panel of nutrient transporters to characterize the impact of a number of tyrosine kinase inhibitor anticancer drugs on human stem cell-derived cardiomyocytes. High-content screening and flow cytometry analysis showed diagnostic changes in nutrient transporter expression correlating with glycolysis and oxidative phosphorylation-based cell metabolism in glucose and galactose media. Cluster analysis of RBD binding signatures of drug-treated cells cultured in glucose medium showed good correlation with sensitization of mitochondrial toxicity in cells undergoing oxidative phosphorylation in galactose medium. These data demonstrate the potential for RBD ligands as profiling tools to improve the clinical predictivity of in vitro cell assays for drug toxicity.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Protein-Tyrosine Kinases
/
Carrier Proteins
/
Myocytes, Cardiac
/
Protein Kinase Inhibitors
/
Antineoplastic Agents
Limits:
Humans
Language:
En
Journal:
J Biomol Screen
Journal subject:
BIOLOGIA MOLECULAR
Year:
2014
Document type:
Article
Country of publication:
United States