Identification of 5-nitrofuran-2-amide derivatives that induce apoptosis in triple negative breast cancer cells by activating C/EBP-homologous protein expression.

ABSTRACT: The transcription factor C/EBP-homologous protein (CHOP) is a key component of the terminal unfolded protein response (UPR) that mediates unresolvable endoplasmic reticulum stress-induced apoptosis. CHOP induction is known to cause cancer cell death. Chemicals that induce CHOP expression would thus be valuable as potential cancer therapeutics and as research tools. Here, we identified 5-nitrofuran-2-amide derivatives as small molecule activators of CHOP expression that induced apoptosis in triple negative breast cancer (TNBC) cells. Our preliminary structure-activity relationship studies indicated that compounds with an N-phenyl-5-nitrofuran-2-carboxamide skeleton were particularly potent inducers of TNBC cell apoptosis. The compounds activate CHOP expression via the PERK-eIF2α-ATF4 branch

SUBMITTER: Duan H 

PROVIDER: S-EPMC5567983 | biostudies-literature | 2015 Aug

REPOSITORIES: biostudies-literature