A novel and specific NADPH oxidase-1 (Nox1) small-molecule inhibitor blocks the formation of functional invadopodia in human colon cancer cells.

ABSTRACT: The NADPH oxidase (Nox) proteins catalyze the regulated formation of reactive oxygen species (ROS), which play key roles as signaling molecules in several physiological and pathophysiological processes. ROS generation by the Nox1 member of the Nox family is necessary for the formation of extracellular matrix (ECM)-degrading, actin-rich cellular structures known as invadopodia. Selective inhibition of Nox isoforms can provide reversible, mechanistic insights into these cellular processes in contrast to scavenging or inhibition of ROS production. Currently no specific Nox inhibitors have been described. Here, by high-throughput screening, we identify a subset of phenothiazines, 2-acetylphenothiazine (here referred to as ML171) (and its related 2-(trifluoromethyl)-phenothiazine) as nanomolar,

SUBMITTER: Gianni D 

PROVIDER: S-EPMC2955773 | biostudies-literature | 2010 Oct

REPOSITORIES: biostudies-literature