Cryptotanshinone inhibits macrophage migration by impeding F-actin polymerization and filopodia extension

We evaluated the anti-inflammatory effects of cryptotanshinone and tanshinone IIA, two major tanshinones isolated from Salvia miltiorrhiza, on chemoattractant-induced cell migration in RAW264.7 macrophages. Results showed that cryptotanshinone inhibited cell migration toward complement 5a (C5a) and macrophage inflammatory protein-1alpha (MIP-1alpha) in a concentration-dependent manner. In contrast, tanshinone IIA displayed less or even no effect on cell migration evoked by these chemoattractants. Both C5a- and MIP-1alpha-induced migration were clearly inhibited by cytochalasin B (an inhibitor of actin polymerization), but not by colchicine (an inhibitor of microtubule polymerization). Fluorescence staining demonstrated that cryptotanshinone as well as cytochalasin B, effectively reversed cell polarization and filopodia extension induced by both chemoattractants. Furthermore, C5a-evoked increase in F-actin fluorescence intensity was significantly suppressed by cryptotanshinone. Based on these observations, we suggest that cryptotanshinone exerts anti-migrating activity possibly by impeding F-actin polymerization and filopodia formation.