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  • Conflict of interest statement br The authors declared no co

    2020-08-12

    Conflict of interest statement
    The authors declared no conflicts of interest.
    Gandin, V., Khalkar, P., Braude, J., Fernandes, A.P., 2018. Organic selenium compounds as potential chemotherapeutic agents for improved cancer treatment. Free Radic. Biol. Med. 127, 80-97.
    Jose, G.M., Raghavankutty, M., Kurup, G.M., 2018. Sulfated polysaccharides from Padina tetrastromatica induce apoptosis in HeLa A 769662 through ROS triggered mitochondrial pathway. Process. Biochem. 68, 197-204.
    ACCEPTED MANUSCRIPT
    Ma, S., Wang, C., Guo, M., 2018. Changes in structure and antioxidant activity of beta-lactoglobulin by ultrasound and enzymatic treatment. Ultrason. Sonochem. 43, 227-236.
    Pescuma, M., Hébert, E.M., Font, G., Saavedra, L., Mozzi, F., 2019. Hydrolysate of β-lactoglobulin by Lactobacillus delbrueckii subsp. bulgaricus CRL 656 suppresses the immunoreactivity of β-lactoglobulin as revealed by in vivo assays. Int. Dairy J. 88, 71-78.
    ACCEPTED MANUSCRIPT
    ACCEPTED A 769662 MANUSCRIPT
    Highlight
    This research may provide valuable information for the selection of a chemopreventive agent for the treatment of breast cancer.
    Study on antitumor mechanism of Se-β-Lg will be more thoroughly and comprehensively in various tumor types combining this article.
    To make the experiment more rigorous, we chose two kinds of breast cancer cells (MCF-7, MDA-MB-231) incubated with Se-β-Lg in this research.
    In human breast cancer MCF-7 and MDA-MB-231 cells, apoptosis was induced through the mitochondria-caspase-dependent apoptotic pathway after treatment with Se-β-Lg.
    ACCEPTED MANUSCRIPT
    Antitumor effects of seleno-β-lactoglobulin on human breast cancer MCF-7 and
    Xiaomeng Xua,b,Yingying Fenga, Xiaoyu Chena, Qinjian Wanga,Ting Menga, Anjun Liua,*
    a Key Laboratory of Food Nutrition and Safety, Ministry of Education, College of Food Engineering and Biotechnology, Tianjin University of Science and Technology,Tianjin 300457, PR China
    bQingYunTang Biotech (Beijing) Co., Ltd., No. 14, Zhonghe Street, Beijing Economic-Technological Development Area, Beijing 100176, PR China * Corresponding author. E-mail address: [email protected](A. Liu).
    Conflict of interest statement
    The authors declared no conflicts of interest. International Journal of Biological Macromolecules 136 (2019) 1–12
    Contents lists available at ScienceDirect
    International Journal of Biological Macromolecules
    Antitumor evaluation of carboxymethyl chitosan based norcantharidin conjugates against gastric cancer as novel polymer therapeutics
    Jinhua Chi a, Zhiwen Jiang a,b, Jing Qiao a, Wei Zhang a, Yanfei Peng a,b, Wanshun Liu a, Baoqin Han a,b,
    a Laboratory of Biochemistry and Biomedical Materials, College of Marine Life Sciences, Ocean University of China, Qingdao 266003, PR China
    b Laboratory for Marine Drugs and Bioproducts of Qingdao National Laboratory for Marine Science and Technology, Qingdao 266235, PR China
    Article history:
    Keywords:
    Carboxymethyl chitosan
    Macromolecular derivative
    Norcantharidin
    Angiogenesis
    Gastric cancer 
    Novel polymer-drug conjugates (CNC) were prepared from carboxymethyl chitosan (CMCS) and norcantharidin (NCTD) via amidation reaction and characterized by FTIR and 1H NMR spectroscopy. The aim of this study was to elucidate the antitumor efficacy of CNC on gastric cancer and the possible underlying mechanisms. The CNC con-jugates possessed significant inhibitory effects on the proliferation of SGC-7901 cells and suppressed the migra-tion as well as tube formation of HUVECs. Besides, Hoechst 33258 staining and Annexin V-FITC/PI detection suggested that the conjugates were more effective in triggering apoptosis of SGC-7901 cells compared with free NCTD. Moreover, CNC remarkably reduced systemic toxicity and enhanced the antitumor efficacy in vivo with a tumor suppression rate of 59.57% against SGC-7901 gastric tumor in BALB/c nude mice. Further investiga-tion about the underlying mechanisms indicated that CNC could upregulate expressions of TNF-α and Bax, and downregulate expressions of VEGF, Bcl-2, MMP-2 and MMP-9, thereby inhibiting tumor metastasis and inducing apoptosis in vivo. Overall, our results demonstrated that CNC might be a promising and feasible polymer thera-peutics for gastrointestinal tumor therapy.
    1. Introduction
    Gastric cancer remains one of the most frequent aggressive malig-nancies with high incidence of local recurrence and distant metastasis [1]. Gastrectomy combined with radiation therapy and chemotherapy are effective measures for gastric cancer without distant metastasis [2]. Although the research on gastric cancer has made great advance-ment, local recurrence, hematogenous metastasis and drug resistance are still main reasons for the advanced stage or the failure of the treat-ment [3]. Many gastric cancer patients are diagnosed at an advanced stage with distant metastasis and extremely low five-year survival rates [4]. Metastasis is a process whereby cancer cells spread from a pri-mary site and form tumors at distant sites [5]. It occurs through complex multistep processes and closely relates to cell migration, invasion, adhe-sion, angiogenesis, extracellular matrix (ECM) degradation and base-ment membrane (BM) breakdown [6]. It is worth noting that angiogenesis is the process of developing vasculature and is essential for the growth of tumors and the development of metastases [7]. Angio-genesis is mediated by numerous stimulatory and inhibitory factors [8]. Consequently, development of novel anti-metastasis and anti-