Development of a novel screening assay for inhibitors targeting HIF-1alpha and P300 interaction / 药学学报
Acta Pharmaceutica Sinica
; (12): 849-853, 2014.
Article
in Zh
| WPRIM
| ID: wpr-245004
Responsible library:
WPRO
ABSTRACT
Hypoxia is a general characteristic of most solid malignancies and intimately related to cancer progression. Homeostatic response to hypoxia is primarily mediated by hypoxia inducible factor-1alpha (HIF-1alpha) that elicits transcriptional activity through recruitment P300 coactivator. Targeting the interaction of HIF- alpha and P300 would thus constitute a novel approach for cancer treatment by suppressing tumor angiogenesis and metastasis. Here, a screening assay was developed for inhibitors targeting the interaction between HIF-1alpha and P300. The nucleotide sequence of human HIF-1alpha and P300 were cloned into pBIND and pACT vectors, named pBIND-HIF1alpha and pACT-P300. The interaction of HIF-1alpha and P300 was identified in HEK293 cell using mammalian two-hybrid system. And compound chetomin decreased their interaction in this mammalian two-hybrid system. We further verified HIF-1 inhibition effect of chetomin in U251-HRE cells. Therefore, we established a screening assay combined HIF-1alpha and P300 mammalian two-hybrid system and U251-HRE reporter assay for HIF-1 selective inhibitors.
Full text:
1
Index:
WPRIM
Main subject:
Pharmacology
/
Drug Screening Assays, Antitumor
/
Cell Hypoxia
/
Two-Hybrid System Techniques
/
Indole Alkaloids
/
Disulfides
/
E1A-Associated p300 Protein
/
Hypoxia-Inducible Factor 1, alpha Subunit
/
HEK293 Cells
Type of study:
Diagnostic_studies
/
Prognostic_studies
/
Screening_studies
Limits:
Humans
Language:
Zh
Journal:
Acta Pharmaceutica Sinica
Year:
2014
Type:
Article