@article {1198, title = {Strongylophorine-26, a Rho-dependent inhibitor of tumor cell invasion that reduces actin stress fibers and induces nonpolarized lamellipodial extensions}, journal = {Molecular Cancer Therapeutics}, volume = {4}, number = {5}, year = {2005}, note = {ISI Document Delivery No.: 926DETimes Cited: 6Cited Reference Count: 37}, month = {May}, pages = {772-778}, type = {Article}, abstract = {Strongylophorine-26, a new meroditerpenoid, was recently identified as an inhibitor of cancer cell invasion. This study was undertaken to characterize its mechanism of action. We find that strongylophorine-26 inhibits the motility of MDA-MB-231 breast carcinoma cells on a plastic surface. Upon addition of strongylophorine-26, rapid cell contraction and depolarization occurred, followed by spreading and flattening of the entire cell. Treated cells exhibited increased membrane ruffling throughout and extended lamellipodia in all directions. Strongylophorine-26 induced a decrease in actin stress fibers, a dramatic increase in the size and number of focal adhesions, and the appearance of a dense meshwork of actin filaments around the cell periphery. Strongylophorine-26 caused a transient activation of the small GTPase Rho and treatment with the Rho inhibitor C3 exoenzyme abrogated the anti-invasive activity of strongylophorine-26. These effects are distinct from those of many motility and angiogenesis inhibitors that seem to act by a common mechanism involving the induction of actin stress fibers. This difference in mechanism of action sets strongylophorine-26 apart as an experimental anticancer agent and indicates that pharmacologic inhibition of cell migration may be achieved by mechanisms not involving the stabilization of actin stress fibers.}, keywords = {ACTIVATION, ANGIOGENESIS, CYTOSKELETON, FAMILY, FOCAL ADHESIONS, KINASE, MIGRATION, MOTILITY, PROTEIN, SMALL GTPASE}, isbn = {1535-7163}, url = {://000229102300009}, author = {McHardy, L. M. and Warabi, K. and Andersen, R. J. and Roskelley, C. D. and Roberge, M.} }