Okadaic Acid Is a Potent Angiogenesis Inducer

Okadaic acid, which is a non‐12‐0‐tetradecanoylphorbol‐13‐acetate (TPA)‐type tumor promoter and an inhibitor of protein phosphatases 1 and 2A, induced angiogenesis in the chorioallantoic membrane of the chick embryo. Its potent angiogenic activity was dose‐dependent. The minimum effective dose was 5 fmol/egg and the effective dose for 50% induction was 90 fmol/egg. These results indicated that okadaic acid exhibits angiogenic activity one order of magnitude stronger than that of TPA (reported previously). Moreover, the time‐course of angiogenesis induction by okadaic acid was much slower than that by TPA. The difference is consistent with the time‐courses of other biochemical and biological activities and also various gene expressions induced by okadaic acid and TPA, indicating that the difference in the time‐course is associated with their mechanisms of action. We conclude that okadaic acid induces angiogenesis through a different pathway than does TPA, indicating the existence of a new mechanism of angiogenesis induction.