title: Apocynin derivatives interrupt intracellular signaling resulting in decreased migration in breast cancer cells.
abstract: Cancer cells are defined by their ability to divide uncontrollably and metastasize to secondary sites in the body. Consequently, tumor cell migration represents a promising target for anticancer drug development. Using our high-throughput cell migration assay, we have screened several classes of compounds for noncytotoxic tumor cell migration inhibiting activity. One such compound, apocynin (4-acetovanillone), is oxidized by peroxidases to yield a variety of oligophenolic and quinone-type compounds that are recognized inhibitors of NADPH oxidase and may be inhibitors of the small G protein Rac1 that controls cell migration. We report here that while apocynin itself is not effective, apocynin derivatives inhibit migration of the breast cancer cell line MDA-MB-435 at subtoxic concentrations; the migration of nonmalignant MCF10A breast cells is unaffected. These compounds also cause a significant rearrangement of the actin cytoskeleton, cell rounding, and decreased levels of active Rac1 and its related G protein Cdc42. These results may suggest a promising new route to the development of novel anticancer therapeutics.
authors.affiliation: Department of Biology, Rensselaer Polytechnic Institute, Troy, NY 12180, USA.
authors.forename: Robert F
authors.initials: RF
authors.lastname: Klees
authors.forename: Paul C
authors.initials: PC
authors.lastname: De Marco
authors.forename: Roman M
authors.initials: RM
authors.lastname: Salasznyk
authors.forename: Disha
authors.initials: D
authors.lastname: Ahuja
authors.forename: Michael
authors.initials: M
authors.lastname: Hogg
authors.forename: Sylvain
authors.initials: S
authors.lastname: Antoniotti
authors.forename: Lakshmi
authors.initials: L
authors.lastname: Kamath
authors.forename: Jonathan S
authors.initials: JS
authors.lastname: Dordick
authors.forename: George E
authors.initials: GE
authors.lastname: Plopper