Umbelliprenin Suppresses Angiogenesis Signaling in Skbr-3 Cell Line By Downregulation of Egf/Cocl2 -Mediated Pi3k/Akt/Mapk

Background and objectives: umbelliprenin, a prenylated coumarin from different species of ferula, has demonstrated anti-cancer effects in various types of cancer cells, but the potential molecular mechanisms for the anti-angiogenic activity of umbelliprenin in breast cancer cells have not yet been studied. in this study, we investigated the possible molecular pathways involved in the anti-angiogenic effect of umbelliprenin in egf and cocl2 stimulated skbr-3 breast cancer cells. methods: effects of umbelliprenin on the changes in egfr signaling genes (egfr, pi3k, akt, mtor, s6k, 4ebp1, erk1/2, hif-1α, hif-1β, vegf, vegfr) and proteins (vegf/hif-1α) expression were assayed in skbr-3 via quantitative pcr and western blotting assays. results: umbelliprenin dramatically decreased the living cells in a concentration related manner (ic50=103.9 µm) and non- toxic doses of umbelliprenin ic5 and ic10 (10 and 20 µm, respectively) were used for evaluating in vitro anti-angiogenic effects. umbelliprenin significantly reduced pro-angiogenic akt, erk1, erk2, mtor, s6k, hif-1α, hif-1b, vegf and vegfr mrnas in egf-treated, and akt, erk2, s6k, hif-1α, hif-1b, vegf and vegfr mrnas in cocl2-treated cells. umbelliprenin significantly increased anti-angiogenic 4ebp1 mrna in egf / cocl2-treated cells. it significantly decreased the levels of hif-1α and vegf proteins, in cocl2-treated cells. conclusion: our findings showed that umbelliprenin exhibits anti-angiogenic effects by decreasing the expression of akt/mtor/mapk angiogenesis pathways in egf or cocl2 treated skbr-3 breast cancer cells.