Recognition of galactan components of pectin by galectin-3

Institute of Food Research, Norwich Research Park, Colney, Norwich NR4 7UA, UK.
The FASEB Journal (Impact Factor: 5.04). 11/2008; 23(2):415-24. DOI: 10.1096/fj.08-106617
Source: PubMed


It has been reported that modified forms of pectin possess anticancer activity. To account for this bioactivity, it has been proposed that fragments of pectin molecules can act by binding to and inhibiting the various roles of the mammalian protein galectin 3 (Gal3) in cancer progression and metastasis. Despite this clear molecular hypothesis and evidence for the bioactivity of modified pectin, the structural origins of the "bioactive fragments" of pectin molecules are currently ill defined. By using a combination of fluorescence microscopy, flow cytometry, and force spectroscopy, it has been possible to demonstrate, for the first time, specific binding of a pectin galactan to the recombinant form of human Gal3. Present studies suggest that bioactivity resides in the neutral sugar side chains of pectin polysaccharides and that these components could be isolated and modified to optimize bioactivity.

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Available from: Roy Bongaerts, Oct 05, 2015
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    • "Pectins from okra and potato are rich in RG-I structures (Cheng et al., 2013; Vayssade et al., 2010), which all have antitumor activity. Experimental results from fluorescence microscopy , fluorescence-activated cell sorting (FACS) and atomic force microscopy (AFM) show that galactan from pectin fragments can bind human recombinant Gal-3 (Gunning et al., 2009). The dissociation coefficient between b-D-galactobiose and Gal-3 is 0.33 s À1 (Gunning, Pin, & Morris, 2013). "
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    ABSTRACT: Pectin, a complex class of plant polysaccharides, is composed of a galacturonan backbone and neutral sugar side chains. Natural pectin is reported to prevent colon cancer as a dietary fiber (DF). To enhance its bioavailability and bioactivity, pectin was modified into bioavailable modified pectin fragments (MPs) with low molecular mass. Also, MPs had low degrees of esterification (DE) which is reported to inhibit tumor growth, induce apoptosis, suppress metastasis, and modulate immunological responses. Antitumor activity of MPs chiefly arises from intervention in ligand recognition by galectin-3 (Gal-3). In addition, pectin is a suitable vehicle for anti-cancer drug delivery systems, due to its abundant modifiable functional groups and special physicochemical properties. Here, we summarize the structural features, bio-absorption and antitumor mechanisms and the structure-activity relationship of MPs. We also offer prospects and challenges for developing pectin into nutraceuticals or drugs.
    Trends in Food Science & Technology 04/2015; 44(2). DOI:10.1016/j.tifs.2015.04.001 · 4.65 Impact Factor
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    • "Gunning et al. (2013) confirmed that neutral galactan side chains did selectively bind to recombinant galectin-3. These active fragments can be obtained by enzymatic treatment of isolated RG-I regions from potato pectin (Gunning et al., 2009). "
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    ABSTRACT: Despite enormous efforts that have been made in the search for novel drugs and treatments, cancer continues to be a major public health problem. Moreover, the emergence of resistance to cancer chemotherapy often prevents complete remission. Researchers have thus turned to natural products mainly from plant origin to circumvent resistance. Pectin and pH- or heat-modified pectin have demonstrated chemopreventive and antitumoral activities against some aggressive and recurrent cancers. The focus of this review is to describe how pectin and modified pectin display these activities and what are the possible underlying mechanisms. The failure of conventional chemotherapy to reduce mortality as well as serious side effects make natural products, such as pectin-derived products, ideal candidates for exerting synergism in combination with conventional anticancer drugs.
    Frontiers in Pharmacology 10/2013; 4:128. DOI:10.3389/fphar.2013.00128 · 3.80 Impact Factor
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    • "MCP acts as a ligand for Gal3, which plays a major role in tumor formation and progression [12,21-24]. It has been shown using a combination of fluorescence microscopy, flow cytometry, and atomic force microscopy, that specific binding of a pectin galactan to the recombinant form of human galectin-3 has been physically observed [25]. Moreover, MCP also showed anti-metastatic effects on cancer cells in vitro or in vivo [8,10,11,24,26-28]. "
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    ABSTRACT: Modified citrus pectin (MCP) is known for its anti-cancer effects and its ability to be absorbed and circulated in the human body. In this report we tested the ability of MCP to induce the activation of human blood lymphocyte subsets like T, B and NK-cells. MCP treated human blood samples were incubated with specific antibody combinations and analyzed in a flow cytometer using a 3-color protocol. To test functionality of the activated NK-cells, isolated normal lymphocytes were treated with increasing concentrations of MCP. Log-phase PKH26-labeled K562 leukemic cells were added to the lymphocytes and incubated for 4 h. The mixture was stained with FITC-labeled active form of caspase 3 antibody and analyzed by a 2-color flow cytometry protocol. The percentage of K562 cells positive for PKH26 and FITC were calculated as the dead cells induced by NK-cells. Monosaccharide analysis of the MCP was performed by high-performance anion-exchange chromatography with pulse amperometric detection (HPAEC-PAD). MCP activated T-cytotoxic cells and B-cell in a dose-dependent manner, and induced significant dose-dependent activation of NK-cells. MCP-activated NK-cells demonstrated functionality in inducing cancer cell death. MCP consisted of oligogalacturonic acids with some containing 4,5-unsaturated non-reducing ends. MCP has immunostimulatory properties in human blood samples, including the activation of functional NK cells against K562 leukemic cells in culture. Unsaturated oligogalacturonic acids appear to be the immunostimulatory carbohydrates in MCP.
    BMC Complementary and Alternative Medicine 08/2011; 11(1):59. DOI:10.1186/1472-6882-11-59 · 2.02 Impact Factor
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