Antimetastatic and antitumor effects of benzoquinonoid AC7-1 from Ardisia crispa

An antimetastatic and cytostatic substance, termed AC7-1, was isolated from Ardisia crispa and identified as a benzoquinonoid compound, 2-methoxy-6-tr idecyl-1,4-benzoquinone. It was originally characterized as the potent PAF (platelet-activating factor) receptor-binding antagonist with nonspecific a ntiplatelet effects on platelet aggregation induced by various agonists inc luding PAF, ADP, thrombin and collagen. The nonspecific antiaggregatory pro perties of AC7-1 drew our interest given its possible relationship in integ rin receptor-binding antagonistic activity. The integrin receptor plays an important role in metastasis and thrombosis as the cell surface transmembra ne protein. Based on the aforementioned facts, the antimetastatic activitie s of AC7-1 were examined using various in vitro and in vivo metastasis assa ys. AC7-1 strongly blocked B16-F10 melanoma cell adhesion to extracellular matrix (ECM) and B16-F10 melanoma cell invasion. AC7-1 also remarkably inhi bited pulmonary metastasis and tumor growth in vivo. AC7-1 inhibited B16-F1 0 melanoma cell adhesion to only specific synthetic peptides including RGDS . These findings suggest that antimetastatic activities of AC7-1 can be cau sed by blocking integrin-mediated adherence. We found AC7-1 to be a potenti al candidate for the development of a new antimetastatic drug. (C) 2001 Wil ey-Liss, Inc.