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PLoS One. 2013 Jul 10;8(7):e68808. doi: 10.1371/journal.pone.0068808. Print 2013.

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.

Author information

1
Department of Biology, College of Science, United Arab Emirates University, Alabama, Ain, United Arab Emirates.

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.

CONCLUSION:

Our findings identify Origanummajorana as a promising chemopreventive and therapeutic candidate that modulate breast cancer growth and metastasis.

PMID:
23874773
PMCID:
PMC3707896
DOI:
10.1371/journal.pone.0068808
[Indexed for MEDLINE]
Free PMC Article

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