%0 Journal Article %T Umbelliprenin Suppresses Angiogenesis Signaling in SKBR-3 Cell Line by Downregulation of EGF/CoCl2 -Mediated PI3K/AKT/MAPK %J Research Journal of Pharmacognosy %I - The Iranian Society of Pharmacognosy - Shahid Beheshti University of Medical Sciences %Z 2345-4458 %A Atabakhshian, Roya %A Salami, Siamak %A Mirfakhraie, Reza %A Mahmoodi Khatonabadi, Somayeh %A Sirati-Sabet, Majid %A Gholamali Yaghmaei, Bahram Gholamali %A Ghafghazi, Shiva %A Dowlati Beirami, Amirreza %A Sadat Rezaei, Mitra %A Ziai*, Seyed Ali %D 2021 %\ 01/01/2021 %V 8 %N 1 %P 7-18 %! Umbelliprenin Suppresses Angiogenesis Signaling in SKBR-3 Cell Line by Downregulation of EGF/CoCl2 -Mediated PI3K/AKT/MAPK %K Angiogenesis %K breast cancer %K COCl2 %K EGF %K umbelliprenin %R 10.22127/rjp.2020.119314 %X 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. %U https://www.rjpharmacognosy.ir/article_119314_a44dffd718134ab0ddf69313d84d85ac.pdf