Glycoconjugate Journal

, Volume 29, Issue 4, pp 159–165 | Cite as

Analysis of the neutral polysaccharide fraction of MCP and its inhibitory activity on galectin-3

  • Xiaoge Gao
  • Yuan Zhi
  • Tao Zhang
  • Huiting Xue
  • Xiao Wang
  • Anthony D. Foday
  • Guihua TaiEmail author
  • Yifa ZhouEmail author


The pH-modified citrus pectin (MCP) has been demonstrated to inhibit galectin-3 in cancer progression. The components and structures of MCP related to this inhibition remained unknown. In this paper, we fractionated MCP on DEAE-cellulose column into a homogenous neutral fraction MCP-N (about 20 kDa) and a pectin mixture fraction MCP-A (wide molecular distribution on Sepharose CL-6B chromatography). Both MCP-N and MCP-A inhibited hemagglutination mediated by galectin-3 with minimum inhibition concentration (MIC) 625 and 0.5 μg/ml, respectively. MCP-N was identified to be a type I arabinogalactan (AG-I) with a main chain of β-1→4-galactan. MCP-N was digested by α-L-arabinofuranosidase to give its main chain structure fraction (M-galactan, around 18 kDa), which was more active than the original molecule, MIC 50 μg/ml. The acidic degradation of M-galactan increased the inhibitory activity, MIC about 5 times lower than M-galactan. These results above showed that the functional motif of the β-1→4-galactan fragment might lie in the terminal residues rather than in the internal region of the chain. Therefore, MCP-N and its degraded products might be developed to new potential galectin-3 inhibitors. This is the first report concerning the fractionation of MCP and its components on galectin-3 inhibition. The information provided in this paper is valuable for screening more active galectin-3 inhibitors from natural polysaccharides.


Citrus pectin Galectin-3 inhibitor Arabinogalactan Hemagglutination assay 



This work was supported by the National Natural Science Foundation of China (Nos. 81173605, 31170770).


  1. 1.
    Dumic, J., Dabelic, S., Flögel, M.: Galectin-3: an open-ended story. Biochim Biophys Acta, Gen Subj 1760, 616–635 (2006)CrossRefGoogle Scholar
  2. 2.
    Prieto, V.G., Mourad-Zeidan, A.A., Melnikova, V., Johnson, M.M., Lopez, A., Diwan, A.H., Lazar, A.J.F., Shen, S.S., Zhang, P.S., Reed, J.A., Gershenwald, J.E., Raz, A., Bar-Eli, M.: Galectin-3 expression is associated with tumor progression and pattern of sun exposure in melanoma. Clin Canc Res 12, 6709–6715 (2006)CrossRefGoogle Scholar
  3. 3.
    Nangia-Makker, P., Conklin, J., Hogan, V., Raz, A.: Carbohydrate-binding proteins in cancer, and their ligands as therapeutic agents. Trends Mol Med 8, 187–192 (2002)PubMedCrossRefGoogle Scholar
  4. 4.
    Glinsky, V.V., Huflejt, M.E., Glinsky, G.V., Deutscher, S.L., Quinn, T.P.: Effects of Thomsen-Friedenreich antigen-specific peptide P-30 on β- galactoside-mediated homotypic aggregation and adhesion to the endothelium of MDA-MB-435 human breast carcinoma cells. Cancer Res 60, 2584–2588 (2000)PubMedGoogle Scholar
  5. 5.
    Glinsky, V.V., Glinsky, G.V., Rittenhouse-Olson, K., Huflejt, M.E., Glinskii, O.V., Deutscher, S.L., Quinn, T.P.: The role of Thomsen-Friedenreich antigen in adhesion of human breast and prostate cancer cells to the endothelium. Cancer Res 61, 4851–4857 (2001)PubMedGoogle Scholar
  6. 6.
    Glinsky, V.V., Glinsky, G.V., Glinskii, O.V., Huxley, V.H., Turk, J.R., Mossine, V.V., Deutscher, S.L., Pienta, K.J., Quinn, T.P.: Intravascular metastatic cancer cell homotypic aggregation at the sites of primary attachment to the endothelium. Cancer Res 63, 3805–3811 (2003)PubMedGoogle Scholar
  7. 7.
    Glinsky, V.V., Kiriakova, G., Glinskii, O.V., Mossine, V.V., Mawhinney, T.P., Turk, J.R., Glinskii, A.B., Huxley, V.H., Price, J.E., Glinsky, G.V.: Synthetic galectin-3 inhibitor increases metastatic cancer cell sensitivity to taxol-induced apoptosis in vitro and in vivo. Neoplasia 11, 901–909 (2009)PubMedGoogle Scholar
  8. 8.
    Sörme, P., Kahl-Knutsson, B., Wellmar, U., Magnusson, B.G., Leffler, H., Nilsson, U.J.: Design and synthesis of galectin inhibitors. Methods Enzym 363, 157–169 (2003)CrossRefGoogle Scholar
  9. 9.
    Zou, J., Glinsky, V.V., Landon, L.A., Matthews, L., Deutscher, S.L.: Peptides specific to the galectin-3 carbohydrate recognition domain inhibit metastasis-associated cancer cell adhesion. Carcinog 26, 309–318 (2005)Google Scholar
  10. 10.
    Rabinovich, G.A., Cumashi, A., Bianco, G.A., Ciavardelli, D., Iurisci, I., D'Egidio, M., Piccolo, E., Tinari, N., Nifantiev, N., Iacobelli, S.: Synthetic lactulose amines: Novel class of anticancer agents that induce tumor-cell apoptosis and inhibit galectin-mediated homotypic cell aggregation and endothelial cell morphogenesis. Glycobiol 16, 210–220 (2006)CrossRefGoogle Scholar
  11. 11.
    Nangia-Makker, P., Hogan, V., Honjo, Y., Baccarini, S., Tait, L., Bresalier, R., Raz, A.: Inhibition of human cancer cell growth and metastasis in nude mice by oral intake of modified citrus pectin. J Natl Canc Inst 94, 1854–1862 (2002)CrossRefGoogle Scholar
  12. 12.
    Sathisha, U.V., Jayaram, S., Harish Nayaka, M.A., Dharmesh, S.M.: Inhibition of galectin-3 mediated cellular interactions by pectic polysaccharides from dietary sources. Glycoconj J 24, 497–507 (2007)PubMedCrossRefGoogle Scholar
  13. 13.
    Streetly, M.J., Maharaj, L., Joel, S., Schey, S.A., Gribben, J.G., Cotter, F.E.: GCS-100, a novel galectin-3 antagonist, modulates MCL-1, NOXA, and cell cycle to induce myeloma cell death. Blood 115, 3939–3948 (2010)PubMedCrossRefGoogle Scholar
  14. 14.
    Li, Y., Liu, L., Niu, Y., Feng, J., Sun, Y., Kong, X., Chen, Y., Chen, X., Gan, H., Cao, S., Mei, Q.: Modified apple polysaccharide prevents against tumorigenesis in a mouse model of colitis-associated colon cancer: role of galectin-3 and apoptosis in cancer prevention. Eur J Nutr 51, 107–117 (2012)Google Scholar
  15. 15.
    Vayssade, M., Sengkhamparn, N., Verhoef, R., Delaigue, C., Goundiam, O., Vigneron, P., Voragen, A.G.J., Schols, H.A., Nagel, M.D.: Antiproliferative and proapoptotic actions of okra pectin on B16F10 melanoma cells. Phytother Res 24, 982–989 (2010)PubMedGoogle Scholar
  16. 16.
    Yapo, B.M., Lerouge, P., Thibault, J.F., Ralet, M.C.: Pectins from citrus peel cell walls contain homogalacturonans homogenous with respect to molar mass, rhamnogalacturonan I and rhamnogalacturonan II. Carbohydr Polym 69, 426–435 (2007)CrossRefGoogle Scholar
  17. 17.
    Platt, D., Raz, A.: Modulation of the lung colonization of B16-F1 melanoma cells by citrus pectin. J Natl Canc Inst 84, 438–442 (1992)CrossRefGoogle Scholar
  18. 18.
    Glinsky, V.V., Raz, A.: Modified citrus pectin anti-metastatic properties: one bullet, multiple targets. Carbohydr Res 344, 1788–1791 (2009)PubMedCrossRefGoogle Scholar
  19. 19.
    Kolatsi-Joannou, M., Price, K.L., Winyard, P.J., Long, D.A.: Modified citrus pectin reduces galectin-3 expression and disease severity in experimental acute kidney injury. PLoS One 6, e18683 (2011)PubMedCrossRefGoogle Scholar
  20. 20.
    Yan, J., Katz, A.: PectaSol-C modified citrus pectin induces apoptosis and inhibition of proliferation in human and mouse androgen-dependent and-independent prostate cancer cells. Integr Canc Ther 9, 197–203 (2010)CrossRefGoogle Scholar
  21. 21.
    Kidd, P.M.: A new approach to metastatic cancer prevention: Modified Citrus Pectin (MCP), a unique pectin that blocks cell surface lectins. Alternative Med Rev 1, 4–10 (1996)Google Scholar
  22. 22.
    Gunning, A.P., Bongaerts, R.J.M., Morris, V.J.: Recognition of galactan components of pectin by galectin-3. J FASEB 23, 415–424 (2009)CrossRefGoogle Scholar
  23. 23.
    Zhang, X., Yu, L., Bi, H., Li, X., Ni, W., Han, H., Li, N., Wang, B., Zhou, Y., Tai, G.: Total fractionation and characterization of the water-soluble polysaccharides isolated from Panax ginseng C. A. Meyer. Carbohydr Polymer 77, 544–552 (2009)CrossRefGoogle Scholar
  24. 24.
    Bi, H., Ni, X., Liu, X., Iteku, J., Tai, G., Zhou, Y., Zhao, J.: A novel water-soluble β-(1→6)-D-glucan isolated from the fruit bodies of Bulgaria inquinans (Fries). Carbohydr Res 344, 1254–1258 (2009)PubMedCrossRefGoogle Scholar
  25. 25.
    Vogl, H., Paper, D.H., Franz, G.: Preparation of a sulfated linear (1→4)-β-D-galactan with variable degrees of sulfation. Carbohydr Polymer 41, 185–190 (2000)CrossRefGoogle Scholar
  26. 26.
    Hinz, S.W.A., Verhoef, R., Schols, H.A., Vincken, J.P., Voragen, A.G.J.: Type I arabinogalactan contains β-D-Galp-(1→3)-β-D-Galp structural elements. Carbohydr Res 340, 2135–2143 (2005)PubMedCrossRefGoogle Scholar
  27. 27.
    Lahaye, M., Vigouroux, J., Thibault, J.F.: Endo-β-1,4-d-galactanase from Aspergillus niger var. aculeatus: purification and some properties. Carbohydr Polymer 15, 431–444 (1991)CrossRefGoogle Scholar
  28. 28.
    Inohara, H., Raz, A.: Functional evidence that cell surface Galectin-3 mediates homotypic cell adhesion. Cancer Res 55, 3267–3271 (1995)PubMedGoogle Scholar
  29. 29.
    Tamaki, Y., Konishi, T., Fukuta, M., Tako, M.: Isolation and structural characterisation of pectin from endocarp of Citrus depressa. Food Chem 107, 352–361 (2008)CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  • Xiaoge Gao
    • 1
    • 2
  • Yuan Zhi
    • 1
    • 2
  • Tao Zhang
    • 1
    • 2
  • Huiting Xue
    • 1
    • 2
  • Xiao Wang
    • 1
    • 2
  • Anthony D. Foday
    • 1
    • 2
  • Guihua Tai
    • 1
    • 2
    Email author
  • Yifa Zhou
    • 1
    • 2
    Email author
  1. 1.School of Life SciencesNortheast Normal UniversityChangchunPeople’s Republic of China
  2. 2.State Key Laboratory of Natural and Biomimetic DrugsPeking UniversityBeijingPeople’s Republic of China

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