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

被引:54
作者
Al Dhaheri, Yusra [1 ]
Attoub, Samir [2 ]
Arafat, Kholoud [2 ]
AbuQamar, Synan [1 ]
Viallet, Jean [3 ]
Saleh, Alaaeldin [4 ]
Al Agha, Hala [4 ]
Eid, Ali [4 ]
Iratni, Rabah [1 ]
机构
[1] United Arab Emirates Univ, Coll Sci, Dept Biol, Alabama, Ain, U Arab Emirates
[2] United Arab Emirates Univ, Fac Med & Hlth Sci, Dept Pharmacol & Therapeut, Alabama, Ain, U Arab Emirates
[3] Univ Grenoble 1, INSERM, U823, Grenoble, France
[4] Qatar Univ, Coll Arts & Sci, Dept Biol & Environm Sci, Doha, Qatar
来源
PLOS ONE | 2013年 / 8卷 / 07期
关键词
E-CADHERIN EXPRESSION; MATRIX METALLOPROTEINASES; TUMOR-GROWTH; PHOSPHATIDYLINOSITOL; 3-KINASE; INVASIVE GROWTH; E-SELECTIN; IN-VITRO; MDA-MB-231; ANGIOGENESIS; MIGRATION;
D O I
10.1371/journal.pone.0068808
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Background: 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-alpha-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 I kappa B, downregulates the nuclear level of NF kappa B 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.
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页数:17
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