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Inhibitory Effect of Melatonin on Hypoxia-Induced Vasculogenic Mimicry Via Suppressing Epithelial-Mesenchymal Transition (Emt) in Breast Cancer Stem Cells. Publisher Pubmed



Maroufi NF1, 2, 3 ; Amiri M4 ; Dizaji BF5 ; Vahedian V6, 7 ; Akbarzadeh M8 ; Roshanravan N9 ; Haiaty S2 ; Nouri M1 ; Rashidi MR1
Authors
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Authors Affiliations
  1. 1. Stem Cell and Regenerative Medicine Institute, Tabriz University of Medical Sciences, Tabriz, Iran
  2. 2. Department of Biochemistry and Clinical Laboratories, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
  3. 3. Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran
  4. 4. Department of Medical Laboratory Science, Faculty of Paramedical Science, Jiroft University of Medical Sciences, Jiroft, Iran
  5. 5. Faculty of Pharmacy, Eastern Mediterranean University, Famagusta, North Cyprus Via Mersin10, 99628, Turkey
  6. 6. Research Club of Tums Preclinical Core Facility (TPCF), Tehran University of Medical Science (TUMS), Tehran, Iran
  7. 7. Department of Medical Laboratory Sciences, Faculty of Medicine, Islamic Azad University (IAU), Sari, Iran
  8. 8. Department of Biochemistry, Erasmus University Medical Center, Rotterdam, Netherlands
  9. 9. Cardiovascular Research Center, Tabriz University of Medical Sciences, Tabriz, Iran

Source: European Journal of Pharmacology Published:2020


Abstract

Vasculogenic mimicry (VM) play an important role in breast cancer metastasis and anti- angiogenic drugs resistance. Hypoxia, the epithelial-mesenchymal transition (EMT), and cancer stem cells (CSCs) are known as essential factors for VM formation. Also, melatonin is an amino acid-derived hormone with many anti-tumor effects. Despite the antitumor effects of melatonin, its effect on VM formation in breast cancer has not been considered yet, so we investigated the effect of melatonin on VM formation through EMT process under hypoxia conditions in breast CSCs. The CSCs percentage and VM formation were determined in MCF-7 and MDA-MB-231, respectively. Also, analysis of HIF-1α expression under hypoxia in MDA-MB-231 and MCF-7 cell lines was performed using Western blot. The effect of melatonin on the VM formation, invasion, and migration was also investigated. Moreover, the effect of melatonin on the expression EMT markers was evaluated. CD44+ CD24-phenotype as CSCs marker in MDA-MB-231 cell line, was 80.8%, while it was 11.1% in MCF-7 cell line. HIF-1α expression was up-regulated in the VM-positive breast cancer cell line MDA-MB-231, and consequently, affected the expression of the EMT markers E-cadherin, vimentin, snail, and MMP9. Melatonin had significant effect on EMT and formations of VM in breast CSCs. Melatonin could prevent the formation of VM by affecting the important molecules involved in the formation of VM structures and the EMT. Moreover, our data clearly showed that, melatonin represents molecule with significant anti-cancer activities that may potentially optimize the management of breast cancer through the overcoming drug resistance in anti-angiogenic drugs. © 2020 Elsevier B.V.