title: Anti-metastatic and anti-tumor growth effects of Origanum majorana on highly metastatic human breast cancer cells: inhibition of NFκB signaling and reduction of nitric oxide production.
abstract: BACKGROUND
  We have recently reported that Origanummajorana exhibits anticancer activity by promoting cell cycle arrest and apoptosis of the metastatic MDA-MB-231 breast cancer cell line. Here, we extended our study by investigating the effect of O. majorana on the migration, invasion and tumor growth of these cells.
  
  
  RESULTS
  We demonstrate that non-cytotoxic concentrations of O. majorana significantly inhibited the migration and invasion of the MDA-MB-231 cells as shown by wound-healing and matrigel invasion assays. We also show that O. majorana induce homotypic aggregation of MDA-MB-231 associated with an upregulation of E-cadherin protein and promoter activity. Furthermore, we show that O. majorana decrease the adhesion of MDA-MB-231 to HUVECs and inhibits transendothelial migration of MDA-MB-231 through TNF-α-activated HUVECs. Gelatin zymography assay shows that O. majorana suppresses the activities of matrix metalloproteinase-2 and -9 (MMP-2 and MMP-9). ELISA, RT-PCR and Western blot results revealed that O. majorana decreases the expression of MMP-2, MMP-9, urokinase plasminogen activator receptor (uPAR), ICAM-1 and VEGF. Further investigation revealed that O. majorana suppresses the phosphorylation of IκB, downregulates the nuclear level of NFκB and reduces Nitric Oxide (NO) production in MDA-MB-231 cells. Most importantly, by using chick embryo tumor growth assay, we also show that O. majorana promotes inhibition of tumor growth and metastasis in vivo.
  
  
  CONCLUSIONS
  Our findings identify Origanummajorana as a promising chemopreventive and therapeutic candidate that modulate breast cancer growth and metastasis.
authors.affiliation: Department of Biology, College of Science, United Arab Emirates University, Alabama, Ain, United Arab Emirates.
authors.forename: Yusra
authors.initials: Y
authors.lastname: Al Dhaheri
authors.forename: Samir
authors.initials: S
authors.lastname: Attoub
authors.forename: Kholoud
authors.initials: K
authors.lastname: Arafat
authors.forename: Synan
authors.initials: S
authors.lastname: Abuqamar
authors.forename: Jean
authors.initials: J
authors.lastname: Viallet
authors.forename: Alaaeldin
authors.initials: A
authors.lastname: Saleh
authors.forename: Hala
authors.initials: H
authors.lastname: Al Agha
authors.forename: Ali
authors.initials: A
authors.lastname: Eid
authors.forename: Rabah
authors.initials: R
authors.lastname: Iratni
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology*; D049109:Cell Proliferation / Q000187:drug effects*; D002478:Cells, Cultured; D002642:Chick Embryo; D005260:Female; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects / Q000502:physiology; D006801:Humans; D016328:NF-kappa B / Q000378:metabolism*; D009362:Neoplasm Metastasis; D009569:Nitric Oxide / Q000378:metabolism*; D031341:Origanum / Q000737:chemistry; D010936:Plant Extracts / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D016328:NF-kappa B; D010936:Plant Extracts; D009569:Nitric Oxide