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

BackgroundWe 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.ResultsWe 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.ConclusionOur findings identify Origanum majorana as a promising chemopreventive and therapeutic candidate that modulate breast cancer growth and metastasis.

Isolation and identification of chemical constituents from Origanum majorana and investigation of antiproliferative and antioxidant activities

“…Previous work revealed that O. majorana essential oils exhibited antioxidant, antifungal, antimicrobial and antibacterial activities. Origanum majorana ethanolic extract also showed the antimetastatic and antitumor growth effects on human breast cancer cells . Ethanol extract of O. majorana leaves exhibited an anti‐proliferative effect and high antioxidant activity .…”

“…Origanum majorana ethanolic extract also showed the antimetastatic and antitumor growth effects on human breast cancer cells. 49 Ethanol extract of O. majorana leaves exhibited an anti-proliferative effect and high antioxidant activity. 50 Quantitative analysis of arbutin in O. majorana has been presented.…”

Origanum majorana Essential Oil Triggers p38 MAPK-Mediated Protective Autophagy, Apoptosis, and Caspase-Dependent Cleavage of P70S6K in Colorectal Cancer Cells

“…Hence, the use of essential oils as a source of potent anticancer compounds has gained a great deal of interest in the field of cancer therapy in recent years. We and others have previously extensively documented the anticancer activities of Origanum majorana ethanolic extract against various types of cancer including breast [17,18], colon [19], and liver [34]. However, to the best of our knowledge, no literature data on the anticancer activity of Origanum majorana essential oil are available.…”

Origanum majoranaEssential Oil Lacks Mutagenic Activity in theSalmonella/Microsome and Micronucleus Assays

“…O. majorana essential oil was also able to partially prevent the ethanol-induced decline in sperm quality, testosterone levels, and the weight of reproductive organs in male rats [2]. Previous studies have reported the potential use of O. majorana ethanolic extract as anticancer agent [10, 11], whereas the tea extract has been shown to have immunostimulant, antigenotoxic and antimutagenic properties [3, 12]. These activities are attributed to the chemical composition, which is characterized as rich in flavonoids and terpenoids [13].…”