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      The natural compound magnolol inhibits invasion and exhibits potential in human breast cancer therapy

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          Abstract

          Invasion and metastasis are the main causes of treatment failure and death in breast cancer. Thus, novel invasion-based therapies such as those involving natural agents are urgently required. In this study, we examined the effects of magnolol (Mag), a compound extracted from medicinal herbs, on breast cancer cells in vitro and in vivo. Highly invasive cancer cells were found to be highly sensitive to treatment. Mag markedly inhibited the activity of highly invasive MDA-MB-231 cells. Furthermore, Mag significantly downregulated matrix metalloproteinase-9 (MMP-9) expression, an enzyme critical to tumor invasion. Mag also inhibited nuclear factor-κB (NF-κB) transcriptional activity and the DNA binding of NF-κB to MMP-9 promoter. These results indicate that Mag suppresses tumor invasion by inhibiting MMP-9 through the NF-κB pathway. Moreover, Mag overcame the promoting effects of phorbol 12-myristate 13-acetate (PMA) on the invasion of MDA-MB-231 cells. Our findings reveal the therapeutic potential and mechanism of Mag against cancer.

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          Most cited references36

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          Breast cancer metastasis: markers and models.

          Breast cancer starts as a local disease, but it can metastasize to the lymph nodes and distant organs. At primary diagnosis, prognostic markers are used to assess whether the transition to systemic disease is likely to have occurred. The prevailing model of metastasis reflects this view--it suggests that metastatic capacity is a late, acquired event in tumorigenesis. Others have proposed the idea that breast cancer is intrinsically a systemic disease. New molecular technologies, such as DNA microarrays, support the idea that metastatic capacity might be an inherent feature of breast tumours. These data have important implications for prognosis prediction and our understanding of metastasis.
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            New signals from the invasive front.

            Approximately 90% of all cancer deaths arise from the metastatic spread of primary tumours. Of all the processes involved in carcinogenesis, local invasion and the formation of metastases are clinically the most relevant, but they are the least well understood at the molecular level. Revealing their mechanisms is one of the main challenges for exploratory and applied cancer research. Recent experimental progress has identified a number of molecular pathways and cellular mechanisms that underlie the multistage process of metastasis formation: these include tumour invasion, tumour-cell dissemination through the bloodstream or the lymphatic system, colonization of distant organs and, finally, fatal outgrowth of metastases.
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              Molecular mechanisms of glioma invasiveness: the role of proteases.

              Jasti Rao (2003)
              The invasive nature of brain-tumour cells makes an important contribution to the ineffectiveness of current treatment modalities, as the remaining tumour cells inevitably infiltrate the surrounding normal brain tissue, which leads to tumour recurrence. Such local invasion remains an important cause of mortality and underscores the need to understand in more detail the mechanisms of tumour invasiveness. Several proteases influence the malignant characteristics of gliomas--could their inhibition prove to be a useful therapeutic strategy?
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                Author and article information

                Journal
                Sci Rep
                Sci Rep
                Scientific Reports
                Nature Publishing Group
                2045-2322
                14 November 2013
                2013
                : 3
                : 3098
                Affiliations
                [1 ]School of Life Sciences, Tsinghua University , Beijing, 100084, China
                [2 ]The Shenzhen Key Laboratory of Gene & Antibody Therapy, State Key Laboratory of Health Science & Technology (prep), Center for Biotechnology & Biomedicine and Division of Life & Health Sciences, Graduate School at Shenzhen, Tsinghua University , Shenzhen, Guangdong, 518055, China
                [3 ]National Laboratory of Biomacromolecules, Institute of Biophysics , Chinese Academy of Sciences, Beijing, 100101, China
                [4 ]Division of Molecular Carcinogenesis and Targeted Therapy for Cancer, State Key Laboratory of Biomembrane and Membrane Biotechnology, Institute of Zoology , Chinese Academy of Sciences, Beijing, 100101, China
                [5 ]These authors contributed equally to this work.
                Author notes
                Article
                srep03098
                10.1038/srep03098
                3827615
                24226295
                796bbcc2-4229-4672-81b8-fdfbba7df6a5
                Copyright © 2013, Macmillan Publishers Limited. All rights reserved

                This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivs 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-nd/3.0/

                History
                : 08 July 2013
                : 15 October 2013
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