Wondonin, a novel compound, inhibits hypoxia-induced angiogenesis through hypoxia-inducible factor 1 alpha.

Hypoxia regulates a variety of transcription factors including HIF-1, which has been considered a target for anti-angiogenic therapy. While searching for a novel anti-angiogenic agent that would inhibit HIF-1 activity, we identified wondonin, a new bis imidazole purified from an association of the sponges Poecillastra wondoensis. Wondonin significantly decreased hypoxia-induced HIF-1alpha protein and VEGF expression and inhibited angiogenesis in vitro and in vivo. Furthermore, wondonin down-regulated HIF-1alpha protein through the increased interaction with the pVHL in immortalized human keratinocyte cell line. Wondonin also decreased the immunoreactivities of CD31 and VEGF in epidermal hyperplasia in mice. Taken together, these results suggested that wondonin had the potential to become the anti-angiogenic therapeutic agent to target HIF-1alpha.