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      Extract from Astragalus membranaceus inhibit breast cancer cells proliferation via PI3K/AKT/mTOR signaling pathway

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          Abstract

          Background

          Astragalus membranaceus (AM) is a commonly used herb in traditional Chinese medicine (TCM), which has been used as an essential tonic to treat various diseases for more than 2000 years. In this study, we aimed to investigate the biological effects of extract from AM on breast cancer cell and its mechanism.

          Methods

          To prepare the extract, dried AM were ground and extracted with water extraction-ethanol supernatant method. Then the main isoflavones in the extract was detect by HPLC analysis. Furthermore, the anti-proliferative activity of AM extract was examined by MTT assay and morphological observation. Cell apoptosis was evaluated with flow cytometric analysis. The expressions of total and phosphorylated PI3K, GS3Kβ, Akt and mTOR were determined by western blot analysis.

          Results

          HPLC analysis demonstrated that AM extract contained with four kinds of isoflavones, campanulin, ononin, calycosin and formononetin. The MTT test and morphological observation indicated that cells proliferation of MCF-7, SK-BR-3 and MDA-MB-231were inhibited by AM extract in a dose dependent manner. Furthermore, flow cytometric analysis displayed that after treated with 25 μg/ml and 50 μg/ml AM extract, apoptosis of breast cancer cells was significantly increased as compared with DMSO and blank control group (all p < 0.05). Western blot analysis found that the level of p-PI3K, p-GS3Kβ, p-Akt, and p-mTOR were significantly decreased, but the level of total-mTOR was observably increased as compared with DMSO control group.

          Conclusions

          Taken together, the inhibited cell proliferation and induced cell apoptosis effect of AM extract via PI3K/AKT/mTOR pathway confirmed the anti-tumor potential of AM. Therefore, our findings provide a new insight into anti-cancer effect of AM extract as a promising agent in breast cancer treatment.

          Electronic supplementary material

          The online version of this article (10.1186/s12906-018-2148-2) contains supplementary material, which is available to authorized users.

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          Most cited references29

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          Extrinsic versus intrinsic apoptosis pathways in anticancer chemotherapy.

          Apoptosis or programmed cell death is a key regulator of physiological growth control and regulation of tissue homeostasis. One of the most important advances in cancer research in recent years is the recognition that cell death mostly by apoptosis is crucially involved in the regulation of tumor formation and also critically determines treatment response. Killing of tumor cells by most anticancer strategies currently used in clinical oncology, for example, chemotherapy, gamma-irradiation, suicide gene therapy or immunotherapy, has been linked to activation of apoptosis signal transduction pathways in cancer cells such as the intrinsic and/or extrinsic pathway. Thus, failure to undergo apoptosis may result in treatment resistance. Understanding the molecular events that regulate apoptosis in response to anticancer chemotherapy, and how cancer cells evade apoptotic death, provides novel opportunities for a more rational approach to develop molecular-targeted therapies for combating cancer.
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            Incidence and Mortality and Epidemiology of Breast Cancer in the World.

            Breast cancer is the most common malignancy in women around the world. Information on the incidence and mortality of breast cancer is essential for planning health measures. This study aimed to investigate the incidence and mortality of breast cancer in the world using age-specific incidence and mortality rates for the year 2012 acquired from the global cancer project (GLOBOCAN 2012) as well as data about incidence and mortality of the cancer based on national reports. It was estimated that 1,671,149 new cases of breast cancer were identified and 521,907 cases of deaths due to breast cancer occurred in the world in 2012. According to GLOBOCAN, it is the most common cancer in women, accounting for 25.1% of all cancers. Breast cancer incidence in developed countries is higher, while relative mortality is greatest in less developed countries. Education of women is suggested in all countries for early detection and treatment. Plans for the control and prevention of this cancer must be a high priority for health policy makers; also, it is necessary to increase awareness of risk factors and early detection in less developed countries.
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              Review of the botanical characteristics, phytochemistry, and pharmacology of Astragalus membranaceus (Huangqi).

              Astragalus membranaceus is one of the most widely used traditional Chinese herbal medicines. It is used as immune stimulant, tonic, antioxidant, hepatoprotectant, diuretic, antidiabetic, anticancer, and expectorant. The current paper reviews the botanical characteristics, phytochemistry, and pharmacology of Astragali Radix. Information on Astragali Radix was gathered via the Internet (using Google Scholar, Baidu Scholar, Elsevier, ACS, Medline Plus, CNKI, and Web of Science) as well as from libraries and local books. More than 100 compounds, including flavonoids, saponins, polysaccharides, and amino acids, have so far been identified, and the various biological activities of the compounds have been reported. As an important traditional Chinese medicine, further studies on Astragali Radix can lead to the development of new drugs and therapies for various diseases. The improvement of its utilization should be studied further.
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                Author and article information

                Contributors
                +86 592 5579628 , xuleqin@163.com
                Journal
                BMC Complement Altern Med
                BMC Complement Altern Med
                BMC Complementary and Alternative Medicine
                BioMed Central (London )
                1472-6882
                9 March 2018
                9 March 2018
                2018
                : 18
                : 83
                Affiliations
                [1 ]ISNI 0000 0004 1790 1622, GRID grid.411504.5, Department of Chest and Breast Surgery, Xiamen Hospital of Traditional Chinese Medicine, , Fujian University of Traditional Chinese Medicine, ; 1739 Xianyue Road, Xiamen, 361009 People’s Republic of China
                [2 ]ISNI 0000 0004 1790 1622, GRID grid.411504.5, Department of Pharmacy, Xiamen Hospital of Traditional Chinese Medicine, , Fujian University of Traditional Chinese Medicine, ; 1739 Xianyue Road, Xiamen, 361009 People’s Republic of China
                [3 ]ISNI 0000 0004 1790 1622, GRID grid.411504.5, Department of Science and Education, Xiamen Hospital of Traditional Chinese Medicine, , Fujian University of Traditional Chinese Medicine, ; 1739 Xianyue Road, Xiamen, 361009 People’s Republic of China
                Article
                2148
                10.1186/s12906-018-2148-2
                5845298
                29523109
                22039261-46c1-4f3f-9a3f-ca0bcfc04f99
                © The Author(s). 2018

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 1 July 2017
                : 28 February 2018
                Funding
                Funded by: National Natural Science Foundation of China
                Award ID: No. 81603642
                Funded by: Natural Science Foundation of Fujian Province, China
                Award ID: No. 2014D013
                Award Recipient :
                Funded by: Science and Technology Planning Projects of Xiamen Science & Technology Bureau, China
                Award ID: No. 3502Z20154052
                Award Recipient :
                Funded by: FundRef http://dx.doi.org/10.13039/501100001809, National Natural Science Foundation of China;
                Award ID: 81704094
                Award Recipient :
                Categories
                Research Article
                Custom metadata
                © The Author(s) 2018

                Complementary & Alternative medicine
                astragalus membranaceus,extract,breast cancer,apoptosis,pi3k,akt
                Complementary & Alternative medicine
                astragalus membranaceus, extract, breast cancer, apoptosis, pi3k, akt

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