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.
Chiou
Wen-Fei
WF
National Research Institute of Chinese Medicine, Taipei, Taiwan, ROC. wfchiou@nricm.edu.tw
Don
Ming-Jaw
MJ
D045784:Abietanes; D000199:Actins / Q000378:metabolism*; D000893:Anti-Inflammatory Agents; D002465:Cell Movement / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D002630:Chemotactic Factors / Q000494:pharmacology; D015936:Complement C5a / Q000494:pharmacology; D003599:Cytoskeleton / Q000378:metabolism; D004365:Drugs, Chinese Herbal / Q000494:pharmacology; D005434:Flow Cytometry; D005456:Fluorescent Dyes; D006801:Humans; D019402:Macrophage Inflammatory Proteins / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects* / Q000648:ultrastructure; D010616:Phenanthrenes / Q000494:pharmacology*; D011554:Pseudopodia / Q000187:drug effects*
D045784:Abietanes; D000199:Actins; D000893:Anti-Inflammatory Agents; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D002630:Chemotactic Factors; D004365:Drugs, Chinese Herbal; D005456:Fluorescent Dyes; D019402:Macrophage Inflammatory Proteins; D010616:Phenanthrenes; C021751:tanshinone; C037886:cryptotanshinone; D015936:Complement C5a