A Phenotypic Cell-Binding Screen Identifies a Novel Compound Targeting Triple-Negative Breast Cancer.
Luxi ChenChao LongJonghae YounJiyong LeePublished in: ACS combinatorial science (2018)
We describe a "phenotypic cell-binding screen" by which therapeutic candidate targeting cancer cells of a particular phenotype can be isolated without knowledge of drug targets. Chemical library beads are incubated with cancer cells of the phenotype of interest in the presence of cancer cells lacking the phenotype of interest, and then the beads bound to only cancer cells of the phenotype of interest are selected as hits. We have applied this screening strategy in discovering a novel compound (LC129-8) targeting triple-negative breast cancer (TNBC). LC129-8 displayed highly specific binding to TNBC in cancer cell lines and patient-derived tumor tissues. LC129-8 exerted anti-TNBC activity by inducing apoptosis, inhibiting proliferation, reversing epithelial-mesenchymal transition, downregulating cancer stem cell activity and blocking in vivo tumor growth.
Keyphrases
- epithelial mesenchymal transition
- signaling pathway
- single cell
- cancer therapy
- cancer stem cells
- simultaneous determination
- high throughput
- cell therapy
- healthcare
- oxidative stress
- liquid chromatography
- papillary thyroid
- emergency department
- gene expression
- transforming growth factor
- endoplasmic reticulum stress
- dna binding
- genome wide
- young adults
- solid phase extraction
- mesenchymal stem cells
- transcription factor
- cell proliferation
- tandem mass spectrometry
- gas chromatography