Okadaic acid is a potent angiogenesis inducer.
Okadaic acid, which is a non-12-O-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.
Division of Cancer Therapeutics, Tokyo Metropolitan Institute of Medical Science.
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Oikawa
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Suganuma
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Ashino-Fuse
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Shimamura
D000818:Animals; D002273:Carcinogens / Q000633:toxicity*; D002642:Chick Embryo; D002823:Chorion / Q000187:drug effects; D004988:Ethers, Cyclic / Q000037:antagonists & inhibitors / Q000633:toxicity*; D009389:Neovascularization, Pathologic / Q000139:chemically induced* / Q000196:embryology; D019319:Okadaic Acid; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013997:Time Factors
D002273:Carcinogens; D004988:Ethers, Cyclic; D019319:Okadaic Acid; D013755:Tetradecanoylphorbol Acetate