Petasiphenol, a polyphenolic compound from a Japanese vegetable (Petasites japonicus) which is a DNA polymerase lambda selective inhibitor, was demonstrated as a potent antiangiogenic agent in this study. Petasiphenol showed suppressive effects on in vitro angiogenesis assays, human umbilical vein endothelial cell (HUVEC) proliferation, tube formation on reconstituted basement membrane and chemotaxis in a dose-dependent manner (10-100 microM). However, treatment of HUVEC with petasiphenol did not affect 72 kDa matrix metalloprotease activity at these concentrations. Petasiphenol at higher 50 microM also suppressed microvessel outgrowth in ex vivo angiogenesis assay using a rat aortic ring. Taken together, petasiphenol could act as a potent antiangiogenic compound for preventing tumor and be useful to design therapeutic agents.