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Background  We have recently reported thatOriganummajoranaexhibits 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 ofO.  majoranaon the migration, invasion and tumor growth of these cells.    Results  We demonstrate that non-cytotoxic concentrations ofO.  majoranasignificantly inhibited the migration and invasion of the MDA-MB-231 cells as shown by wound-healing and matrigel invasion assays. We also show thatO.  majoranainduce homotypic aggregation of MDA-MB-231 associated with an upregulation of E-cadherin protein and promoter activity. Furthermore, we show thatO.  majoranadecrease 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 thatO.  majoranasuppresses the activities of matrix metalloproteinase-2 and -9 (MMP-2 and MMP-9). ELISA, RT-PCR and Western blot results revealed thatO.  majoranadecreases the expression of MMP-2, MMP-9, urokinase plasminogen activator receptor (uPAR), ICAM-1 and VEGF. Further investigation revealed thatO.  majoranasuppresses 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 thatO.  majoranapromotes inhibition of tumor growth and metastasis  in vivo .    Conclusion  Our findings identifyOriganummajoranaas a promising chemopreventive and therapeutic candidate that modulate breast cancer growth and metastasis.

plos one

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