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‐tridecyl‐1,4‐benzoquinone. It was originally characterized as the potent PAF (platelet‐activating factor) receptor‐binding antagonist with nonspecific antiplatelet effects on platelet aggregation induced by various agonists including PAF, ADP, thrombin and collagen. The nonspecific antiaggregatory properties of AC7‐1 drew our interest given its possible relationship in integrin receptor‐binding antagonistic activity. The integrin receptor plays an important role in metastasis and thrombosis as the cell surface transmembrane protein. Based on the aforementioned facts, the antimetastatic activities of AC7‐1 were examined using various in vitro and in vivo metastasis assays. AC7‐1 strongly blocked B16‐F10 melanoma cell adhesion to extracellular matrix (ECM) and B16‐F10 melanoma cell invasion. AC7‐1 also remarkably inhibited pulmonary metastasis and tumor growth in vivo. AC7‐1 inhibited B16‐F10 melanoma cell adhesion to only specific synthetic peptides including RGDS. These findings suggest that antimetastatic activities of AC7‐1 can be caused by blocking integrin‐mediated adherence. We found AC7‐1 to be a potential candidate for the development of a new antimetastatic drug. © 2001 Wiley‐Liss, Inc.

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