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      Chemopreventive Effects of Oplopantriol A, a Novel Compound Isolated from Oplopanax horridus, on Colorectal Cancer

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          Abstract

          Oplopanax horridus is a North American botanical that has received limited investigations. We previously isolated over a dozen of the constituents from O. horridus, and among them oplopantriol A (OPT A) is a novel compound. In this study, we firstly evaluated the in vivo chemoprevention activities of OPT A using the xenograft colon cancer mouse model. Our data showed that this compound significantly suppressed tumor growth with dose-related effects ( p < 0.01). Next, we characterized the compound’s growth inhibitory effects in human colorectal cancer cell lines HCT-116 and SW-480. With OPT A treatment, these malignant cells were significantly inhibited in both a concentration- and time-dependent manner (both p < 0.01). The IC50 was approximately 5 µM for HCT-116 and 7 µM for SW-480 cells. OPT A significantly induced apoptosis and arrested the cell cycle at the G2/M phase. From further mechanism explorations, our data showed that OPT A significantly upregulated the expression of a cluster of genes, especially the tumor necrosis factor receptor family and caspase family, suggesting that the tumor necrosis factor-related apoptotic pathway plays a key role in OPT A induced apoptosis.

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          Most cited references 27

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          Impact of natural products on developing new anti-cancer agents.

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            Establishment of human tumor xenografts in immunodeficient mice.

            Heterotransplantation of human cancer cells or tumor biopsies into immunodeficient rodents (xenograft models) has, for the past two decades, constituted the major preclinical screen for the development of novel cancer therapeutics. Despite limitations, these models have identified clinically efficacious agents, and remain the 'workhorse' of the pharmaceutical industry. However, if therapeutic approaches to treating tumors according to their molecular characteristics are to be achieved, additional new models of human cancer will be required to represent the genetic diversity that exists within tumor histologies. This protocol details a method for establishing xenografts from primary solid-tumor isolates or cells grown in culture. The procedure relies on immunodeficient mice to provide a host for the establishment of human xenografts. The procedure can be completed in 1-2 h with results being obtained in 1-4 months.
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              Ginsenoside Rg3 inhibits colorectal tumor growth through the down-regulation of Wnt/ß-catenin signaling.

              Colorectal cancer (CRC) is one of the most common and deadly malignancies in the world. Most CRCs are initiated by aberrant activation of the Wnt/ß-catenin signaling pathway. Despite the advances in its early diagnosis, optimized surgical approaches, and chemotherapies, the clinical management of advanced CRC requires effective adjuvant agents. Ginsenoside Rg3 is a single compound isolated from American ginseng (Panax quinquefolius L., Araliaceae) and Asian ginseng (Panax ginseng C. A. Meyer). We investigated the anticancer activity of Rg3 on colon cancer cells and its potential molecular mechanism behind Rg3's anticancer activity. We found that Rg3 inhibits cell proliferation and viability of cancer cells in vitro. This inhibitory effect of Rg3 is, at least in part, mediated by blocking nuclear translocation of the ß-catenin protein and hence inhibiting ß-catenin/Tcf transcriptional activity. Allelic deletion of the oncogenic ß-catenin in HCT116 cells renders the cells more sensitive to Rg3-induced growth inhibition. Using the xenograft tumor model of human colon cancer, we have demonstrated that Rg3 effectively inhibits the growth of tumors derived from the human colon cancer cell line HCT116. Histologic examination revealed that Rg3 inhibits cancer cell proliferation, decreases PNCA expression and diminishes nuclear staining intensity of ß-catenin. Taken together, our results strongly suggest that the anticancer activity of Rg3 may be in part caused by blocking the nuclear translocation of ß-catenin in colon cancer cells. This line of investigation may lead to the development of novel therapies in which Rg3 can be used as an effective adjuvant agent for the clinical management of colorectal cancers.
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                Author and article information

                Journal
                Nutrients
                Nutrients
                nutrients
                Nutrients
                MDPI
                2072-6643
                18 July 2014
                July 2014
                : 6
                : 7
                : 2668-2680
                Affiliations
                [1 ]Tang Center for Herbal Medicine Research, The Pritzker School of Medicine, University of Chicago, Chicago, IL 60637, USA; E-Mails: zzhang2@ 123456bsd.uchicago.edu (Z.Z.); CYu@ 123456dacc.uchicago.edu (C.Y.); zhangchunfeng67@ 123456163.com (C.-F.Z.); longhui804@ 123456163.com (X.-H.W.); cpuwxd@ 123456gmail.com (X.-D.W.); sanderson6@ 123456uchicago.edu (S.A.); CYuan@ 123456dacc.uchicago.edu (C.-S.Y.)
                [2 ]Department of Anesthesia & Critical Care, Pritzker School of Medicine, University of Chicago, Chicago, IL 60637, USA
                [3 ]Ben May Department for Cancer Research, Pritzker School of Medicine, University of Chicago, Chicago, IL 60637, USA; E-Mail: wei@ 123456uchicago.edu
                [4 ]Institute of Clinical Pharmacology, Central South University, Changsha 410000, China; E-Mail: endeavor34852@ 123456aliyun.com
                [5 ]State Key Laboratory of Quality Research in Chinese Medicine, and Institute of Chinese Medical Sciences, University of Macau, Macao, China; E-Mail: spli@ 123456umac.mo
                [6 ]Committee on Clinical Pharmacology and Pharmacogenomics, Pritzker School of Medicine, University of Chicago, Chicago, IL 60637, USA
                Author notes
                [* ]Authors to whom correspondence should be addressed; E-Mails: cwang@ 123456dacc.uchicago.edu (C.-Z.W.); spli@ 123456umac.mo (S.-P.L.); Tel.: +1-773-702-0166 (C.-Z.W.); +853-8397-4692 (S.-P.L.); Fax: +1-773-834-0601 (C.-Z.W.); +853-2884-1358 (S.-P.L.).
                Article
                nutrients-06-02668
                10.3390/nu6072668
                4113763
                25045937
                © 2014 by the authors; licensee MDPI, Basel, Switzerland.

                This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license ( http://creativecommons.org/licenses/by/3.0/).

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