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      Morusin shows potent antitumor activity for human hepatocellular carcinoma in vitro and in vivo through apoptosis induction and angiogenesis inhibition

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          Abstract

          Hepatocellular carcinoma (HCC) is one of the most aggressive cancers with high mortality worldwide. Research and development of novel agents for HCC therapy is in demand, urgently. Morusin has been reported to exhibit potential cytotoxic activity in several cancer cell lines. However, whether it has potential antiangiogenic activity especially in HCC remains unclear. In the current study, we found that morusin exerted growth inhibition effects on human HCC cells (HepG2 and Hep3B) in vitro and human HCC cell (HepG2) xenografts in vivo. Moreover, apoptosis induction was observed in a dose-dependent manner after morusin treatment along with an increase in the expression of active caspase-3 and the Bax/Bcl-2 expression ratio. More importantly, morusin inhibited proliferation, migration, and tube formation of human umbilical vein endothelial cells (HUVECs) in vitro and downregulated angiogenic proteins in HCC cells and HUVECs. In vivo, tumor angiogenesis was also attenuated after morusin treatment. In addition, morusin suppressed constitutive as well as IL-6-induced STAT3 phosphorylation in HCC cells and corresponding tumor tissues. Overall, morusin has a potential anticancer effect on human HCC cells in vitro and in vivo by inducing apoptosis and inhibiting anti-angiogenesis. The corresponding mechanism might be associated with the attenuation of the IL-6/STAT3 signaling pathway. Morusin might serve as a promising novel anticancer agent in HCC therapy, and requires further study.

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          Most cited references 42

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          The growth of blood vessels (a process known as angiogenesis) is essential for organ growth and repair. An imbalance in this process contributes to numerous malignant, inflammatory, ischaemic, infectious and immune disorders. Recently, the first anti-angiogenic agents have been approved for the treatment of cancer and blindness. Angiogenesis research will probably change the face of medicine in the next decades, with more than 500 million people worldwide predicted to benefit from pro- or anti-angiogenesis treatments.
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              Cell sensitivity assays: the MTT assay.

              The MTT (3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide) assay is based on the conversion of MTT into formazan crystals by living cells, which determines mitochondrial activity. Since for most cell populations the total mitochondrial activity is related to the number of viable cells, this assay is broadly used to measure the in vitro cytotoxic effects of drugs on cell lines or primary patient cells. In this chapter the protocol of the assay is described including important considerations relevant for each step of the assay as well as its limitations and possible applications.
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                Author and article information

                Journal
                Drug Des Devel Ther
                Drug Des Devel Ther
                Drug Design, Development and Therapy
                Drug Design, Development and Therapy
                Dove Medical Press
                1177-8881
                2017
                16 June 2017
                : 11
                : 1789-1802
                Affiliations
                [1 ]Department of Abdominal Cancer
                [2 ]Laboratory of Lung Cancer, Lung Cancer Center
                [3 ]Laboratory of Experimental Oncology, West China Hospital, West China Clinical Medical School, Sichuan University, Chengdu, People’s Republic of China
                Author notes
                Correspondence: Xiujie Wang, Laboratory of Experimental Oncology, West China Hospital, West China Clinical Medical School, Sichuan University, 37 Guoxue Xiang, Chengdu 610041, People’s Republic of China, Tel/fax +86 28 8516 4018, Email xiujiewang@ 123456scu.edu.cn
                Cheng Yi, Department of Abdominal Cancer, West China Hospital, West China Clinical Medical School, Sichuan University, 37 Guoxue Xiang, Chengdu 610041, People’s Republic of China, Email chengyi_co@ 123456163.com
                [*]

                These authors contributed equally to this work

                Article
                dddt-11-1789
                10.2147/DDDT.S138320
                5481341
                © 2017 Gao et al. This work is published and licensed by Dove Medical Press Limited

                The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.

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                Original Research

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