Author/Authors :
Atabakhshian ، Roya Department of Clinical Biochemistry - School of Medicine - Shahid Beheshti University of Medical Sciences , Salami ، Siamak Department of Clinical Biochemistry - School of Medicine - Shahid Beheshti University of Medical Sciences , Mirfakhraie ، Reza Department of Medical Genetics - School of Medicine - Shahid Beheshti University of Medical Sciences , Mahmoodi Khatonabadi ، Somayeh Department of Clinical Biochemistry - School of Medicine - Shahid Beheshti University of Medical Sciences , Sirati-Sabet ، Majid Department of Clinical Biochemistry - School of Medicine - Shahid Beheshti University of Medical Sciences , Gholamali Yaghmaei ، Bahram Department of Clinical Biochemistry - School of Medicine - Shahid Beheshti University of Medical Sciences , Ghafghazi ، Shiva Department of Pharmacology - School of Medicine - Shahid Beheshti University of Medical Sciences , Dowlati Beirami ، Amirreza Department of Medicinal Chemistry - School of Pharmacy - Shahid Beheshti University of Medical Sciences , Sadat Rezaei ، Mitra Department of Pathology - School of Medicine - Shahid Beheshti University of Medical Sciences , ziai ، Ali Department of Pharmacology - School of Medicine - Shahid Beheshti University of Medical Sciences
Abstract :
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.
Keywords :
Angiogenesis , breast cancer , COCl2 , EGF , umbelliprenin
