Apocynin Derivatives Interrupt Intracellular Signaling Resulting in Decreased Migration in Breast Cancer Cells

Cancer cells are defined by their ability to divide uncontrollablyand metastasize to secondary sites in the body. Consequently,tumor cell migration represents a promising target for anticancerdrug development. Using our high-throughput cell migration assay,we have screened several classes of compounds for noncytotoxictumor cell migration inhibiting activity. One such compound,apocynin (4-acetovanillone), is oxidized by peroxidases to yield avariety of oligophenolic and quinone-type compounds that arerecognized inhibitors of NADPH oxidase and may be inhibitors ofthe small G protein Rac1 that controls cell migration. We reporthere that while apocynin itself is not effective, apocyninderivatives inhibit migration of the breast cancer cell lineMDA-MB-435 at subtoxic concentrations; the migration ofnonmalignant MCF10A breast cells is unaffected. These compoundsalso cause a significant rearrangement of the actin cytoskeleton,cell rounding, and decreased levels of active Rac1 and its relatedG protein Cdc42. These results may suggest a promising new routeto the development of novel anticancer therapeutics