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AuthorAl Dhaheri, Yusra
AuthorAttoub, Samir
AuthorArafat, Kholoud
AuthorAbuQamar, Synan
AuthorViallet, Jean
AuthorSaleh, Alaaeldin
AuthorAl Agha, Hala
AuthorEid, Ali
AuthorIratni, Rabah
Available date2016-03-31T14:00:59Z
Publication Date2013-07
Publication NamePLoS ONE
CitationAl Dhaheri Y, Attoub S, Arafat K, AbuQamar S, Viallet J, Saleh A, et al. (2013) Anti-Metastatic and Anti-Tumor Growth Effects of Origanum majorana on Highly Metastatic Human Breast Cancer Cells: Inhibition of NF?B Signaling and Reduction of Nitric Oxide Production. PLoS ONE 8(7): e68808.
ISSN1932-6203
URIhttp://dx.doi.org/10.1371/journal.pone.0068808
URIhttp://hdl.handle.net/10576/4303
AbstractBackground: We have recently reported that Origanum majorana 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. Conclusion: Our findings identify Origanum majorana as a promising chemopreventive and therapeutic candidate that modulate breast cancer growth and metastasis.
SponsorCollege of Science (UAEU) interdisciplinary research grant to RI and by a Terry Fox research grant to SA.
Languageen
PublisherPublic Library of Science
SubjectBreast cancer
SubjectMetastasis
SubjectNitric Oxide
SubjectCancer treatment
SubjectCancer cell migration
SubjectEmbryos
SubjectCell migration
SubjectAngiogenesis
TitleAnti-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
TypeArticle
Issue Number7
Volume Number8


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