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.
Kang
Y H
YH
Cancer Research Institute, Seoul National University College of Medicine, Seoul, South Korea.
Kim
W H
WH
Park
M K
MK
Han
B H
BH
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000627:therapeutic use*; D016227:Benzoquinones / Q000627:therapeutic use*; D002448:Cell Adhesion / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D004195:Disease Models, Animal; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D008175:Lung Neoplasms / Q000401:mortality / Q000517:prevention & control* / Q000556:secondary; D019684:Magnoliopsida / Q000737:chemistry*; D008297:Male; D008546:Melanoma, Experimental / Q000188:drug therapy / Q000401:mortality; D051379:Mice; D008810:Mice, Inbred C57BL; D009361:Neoplasm Invasiveness / Q000517:prevention & control; D009368:Neoplasm Transplantation; D010455:Peptides / Q000378:metabolism; D008517:Phytotherapy; D016896:Treatment Outcome
C432263:2-methoxy-6-tridecyl-1,4-benzoquinone; D000972:Antineoplastic Agents, Phytogenic; D016227:Benzoquinones; D016326:Extracellular Matrix Proteins; D010455:Peptides