The Angiotensin-Converting Enzyme Inhibitor ‘Enalapril’ Increases the Anti-Proliferative Activity of 5-Fluorouracil in Colorectal Cancer Cells
Asma Mostafapour1, Javad Baharara2, Majid Khazaei3, Amir Avan4, Seyed Mahdi Hassanian51Department of Biology, Mashhad Branch, Islamic Azad University, Mashhad, Iran, 2Department of Biology & Research Center for Animal Development Applied Biology, Mashhad Branch, Islamic Azad University, Mashhad, Iran, 3Department of Physiology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran, 4Department of Medical Genetics, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran, 5Department of Medical Biochemistry, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran Department of Medical Biochemistry, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran,
Objectives: The dysregulation of angiotensin-converting enzyme inhibitor (ACE-I) and its pathway has been reported to be associated with oncogenesis and poor prognosis in colorectal cancer (CRC). Methods: We explored the therapeutic potential of targeting ACE-I through the use of enalapril and investigated its pharmacological interaction with 5-FU in CT26, HT29, and SW480 cells. The anti-proliferative and anti-migratory effects as well as apoptotic activity of this agent on cell cycle have been evaluated by MTT, wound healing assay, and FACS, while the expression of genes was determined through mRNA or protein levels. Results: According to the observations, enalapril has inhibited cell proliferation in a dose-dependent manner and affected the anti-tumor properties of 5-FU via increasing the levels of apoptosis and ROS, as well as through the modulation of antioxidant/oxidant markers. Enalapril has also suppressed cell migration by the perturbation of MMP3/MMP-9 and E-cadherin. The combination of enalapril and 5FU has resulted in decrease in the expression levels of ACE, AT1R, and SMAD-3. Conclusion: Our findings suggested that targeting ACE-I by applying the modulation of angiotensin pathway could increase the activity of 5-FU due to interfering with cell-proliferation, apoptosis, and inflammatory markers, which is indicative of its potential value as a therapeutic option for the treatment of (CRC). Keywords: ACE inhibitor, Enalapril, Colorectal Cancer, Combination therapy
Cite This Article
Mostafapour A, Baharara J, Khazaei M, Avan A, Mahdi Hassanian S. The Angiotensin-Converting Enzyme Inhibitor ‘Enalapril’ Increases the Anti-Proliferative Activity of 5-Fluorouracil in Colorectal Cancer Cells. EJMO. 2021; 5(4): 318-326
Corresponding Author: Javad Baharara