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

[摘要] 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.

[学科分类] 基础医学