Okadaic acid promotes angiogenesis via activation of hypoxia-inducible factor-1.

Okadaic acid, a potent tumor promoter and an inhibitor of protein phosphatase 1 and 2A, has also been characterized as an angiogenic inducer in the chorioallantoic membrane of the chick embryo. To elucidate the roles of okadaic acid on angiogenic processes, we conducted in vitro angiogenesis assays. In this study, we report that okadaic acid potently stimulated tube formation, migration, and invasion of human umbilical vein endothelial cells. Moreover, okadaic acid elevated the activities of hypoxia-inducible factor-1 (HIF-1), which is closely related with the expression of vascular endothelial growth factor. Exposure to okadaic acid markedly increased the HIF-1alpha protein level through up-regulation of translation via activation of Akt and mTOR pathway. Taken together, these results demonstrated that okadaic acid promotes angiogenesis through stimulation of Akt mediated HIF-1alpha translation.