AG311, a small molecule inhibitor of complex I and hypoxia-induced HIF-1α stabilization.

ABSTRACT: Cancer cells have a unique metabolic profile and mitochondria have been shown to play an important role in chemoresistance, tumor progression and metastases. This unique profile can be exploited by mitochondrial-targeted anticancer therapies. A small anticancer molecule, AG311, was previously shown to possess anticancer and antimetastatic activity in two cancer mouse models and to induce mitochondrial depolarization. This study defines the molecular effects of AG311 on the mitochondria to elucidate its observed efficacy. AG311 was found to competitively inhibit complex I activity at the ubiquinone-binding site. Complex I as a target for AG311 was further established by measuring oxygen consumption rate in tumor tissue isolated from AG311-treated mice. Cotreatment of cells and animals with

SUBMITTER: Bastian A 

PROVIDER: S-EPMC5318233 | biostudies-literature | 2017 Mar

REPOSITORIES: biostudies-literature