Tehran University of Medical Sciences Basic & Clinical Cancer Research 2228-6527 12 3 2021 02 15 112 119 Zahra Zare Department of Biology, Farhangian University, Tehran, Iran. Tina Nayerpour Dizaj Department of Medical Biotechnology, Faculty of Modern Sciences, Tabriz University of Medical Sciences, Tabriz, Iran. Armaghan Lohrasbi Department of Biological and Biomedical Sciences, Glasgow Caledonian University, Cowcaddens Road, Glasgow G4 0BA, UK. Zakieh Sadat Sheikhalishahi Department of Physiology, Shahid Sadoghi University of Medical Sciences, Yazd, Iran. Mohammad Panji Department of Cell and Molecular Biology, Faculty of Biological Science, Kharazmi University, Tehran, Iran. Fahimeh Hosseinabadi Biology Department, Faculty of Sciences, Arak University, Arak, Iran. Vajiheh Najafi Research Center for Biochemistry and Nutrition in Metabolic Diseases, Kashan University of Medical Sciences, Kashan, Iran. Omid Abazari Department of Clinical Biochemistry, School of Medicine, Shahid Sadoughi University of Medical Sciences and Health Services, Yazd, Iran. Mojtaba Abbasi Veterinary Medicine, Faculty of Veterinary Medicine, Shahrekord Branch, Islamic Azad University, Shahrekord, Iran. Parisa Khanicheragh Department of Clinical Biochemistry, Lorestan University of Medical Sciences, Khorramabad, Iran. 2020 06 13 Background: Vascular endothelial growth factor (VEGF), matrix metalloproteinase-9 (MMP-9), and E-cadherin play a vital role in the behavior of angiogenesis, metastasis, and invasion of breast tumor cells. Piperine, the main component of Piper Nigrum, has shown anti-cancer properties in various malignancies. This Study investigates the potential effect of piperine on MMP-9, E-cadherin, and VEGF expression in breast cancer MCF-7 cell line. Methods: MTT assay was applied to assess the viability of MCF-7 cells. The mRNA levels of MMP-9, VEGF, and E-cadherin were assayed by qRT-PCR. Western blot was performed to identify the protein level of MMP-9. Results: MTT assay results showed that piperine treatment (5, 10, 25, 50, 75, and 100 μM) for 24 hours effectively inhibited cell viability of MCF-7 cells as compared with the control group. Furthermore, the gene expression of VEGF, MMP-9, and E-cadherin was dose-dependently suppressed by piperine treatment (5, 10 and 25 μM) (P<0.05; P<0.01). The results also indicated that piperine (5, 10, and 25 μM) significantly suppressed MMP-9 protein expression after 24 hours of piperine treatment (P<0.01).   Conclusion: These results suggest that piperine may prevent angiogenesis, migration, and invasion of MCF-7 cells by suppressing MMP-9 and VEGF, and by inducing E-cadherin expression. Hence, it may be a suitable candidate for designing new drugs in cancer therapy. https://bccr.tums.ac.ir/index.php/bccrj/article/view/349