Umbelliprenin Suppresses Angiogenesis Signaling in SKBR-3 Cell Line by Downregulation of EGF/CoCl2 -Mediated PI3K/AKT/MAPK

• Main Authors: Roya Atabakhshian (Author), Siamak Salami (Author), Reza Mirfakhraie (Author), Somayeh Mahmoodi Khatonabadi (Author), Majid Sirati-Sabet (Author), Bahram Gholamali Yaghmaei (Author), Shiva Ghafghazi (Author), Amirreza Dowlati Beirami (Author), Mitra Sadat Rezaei (Author), Seyed Ali Ziai* (Author)
• Format: Book
• Published: Iranian Society of Pharmacognosy, 2021-01-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.
• Notes: 2345-4458; 2345-5977; 10.22127/rjp.2020.119314
• Keywords: angiogenesis; breast cancer; cocl2; egf; umbelliprenin; Pharmacy and materia medica; RS1-441
• Source: Research Journal of Pharmacognosy, Vol 8, Iss 1, Pp 7-18 (2021)

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.