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Inhibition of galectin-3 mediated cellular interactions by pectic polysaccharides from dietary sources

Abstract

Pectic polysaccharides from dietary sources such as Decalepis hamiltonii—swallow root (SRPP), Hemidesmus indicus (HPP), Nigella sativa—black cumin (BCPP), Andrographis serpyllifolia—(APP), Zingiber officinale—ginger (GRPP) and, citrus pectin (CPP) were examined for galectin inhibitory activity. Inhibition of (a) galectin-3 of MDA-MB-231 cells induced hemagglutination of red blood cells; (b) galectin-3 mediated interaction between normal/metastatic human buccal cells (NBC)/(MBC) and; (c) invasion of MDA-MB-231 and MBC in the invasive chamber was assessed. Results indicated that SRPP inhibited hemagglutination at Minimum Inhibitory Concentration (MIC) of 1.86 μg ml−1 equivalent of carbohydrate as apposed to those of BCPP (130 μg ml−1), APP (40 μg ml−1), HPP (40 μg ml−1) and CPP (25 μg ml−1). GRPP even at concentration >1–6 mg ml−1 did not inhibit agglutination. Also SRPP showed ∼15 and 2 fold potent anti hemagglutination activity relative to that of galectin-3 specific sugars—galactose (MIC-27.1 μg ml−1) and lactose (MIC-4.16 μg ml−1) respectively. Further, SRPP at 10 μg ml−1 inhibited agglutination of NBC by galectin-3 of MDA-MB-231 cells. Modified swallow root pectic polysaccharide (MSRPP) of 50 kDa retained anti hemagglutination activity (MIC of 1.03 μg ml−1) and inhibited MDA-MB-231 and MBC invasion by 73 and 50% with an IC50 of 136 and 200 μg ml−1 respectively. Both SRPP and MSRPP induced apoptosis up to 80% at 100 μg ml−1 concentration by activating ∼2 and 8 folds of Caspase-3 activity. Sugar composition analysis and its correlation with the galectin inhibitory property indicated that pectic polysaccharides with higher arabinose and galactose content—arabinogalactan inhibited hemagglutination significantly.

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Abbreviations

SRPP:

swallow root pectic polysaccharide

HPP:

Hemidesmus pectic polysaccharide

BCPP:

black cumin pectic polysaccharide

APP:

Andrographis pectic polysaccharide

GRPP:

ginger pectic polysaccharide

CPP:

citrus pectic polysaccharide

NBC:

normal human buccal cells

MBC:

metastatic human buccal cells

MIC:

Minimum Inhibitory Concentration

MSRPP:

modified swallow root pectic polysaccharide

References

  1. Zoltan-Jones, A., Huang, L., Ghatak, S., Toole, B.P.: Elevated hyaluronan production induces mesenchymal and transformed properties in epithelial cells. J. Biol. Chem. 278, 45801–45810 (2003)

    PubMed  Article  CAS  Google Scholar 

  2. Beuth, J., Ko, H.L., Oette, K., et al.: Inhibition of liver metastasis in mice by blocking hepatocyte lectins with arabinogalactan infusions and D-galactose. J. Cancer Res. Clin. Oncol. 113, 51–55 (1987)

    PubMed  Article  CAS  Google Scholar 

  3. Bresalier, R.S., Yan, P.S., Byrd, J.C., Lotan, R., Raz, A.: Expression of the endogenous galactose-binding protein galectin-3 correlates with the malignant potential of tumors in the central nervous system. Cancer Res. 80, 776–787 (1997)

    CAS  Google Scholar 

  4. Davidson, P.J., Davis, M.J., Patterson, R.J., Ripoche, M.A., Poirier, F., Wang, J.L.: Shuttling of galectin-3 between the nucleus and cytoplasm. Glycobiology 12, 329–337 (2002)

    PubMed  Article  CAS  Google Scholar 

  5. Dharmesh, S.M., Skelton, T.P., Baenziger, J.U.: Co-ordinate and restricted expression of the ProXaa Arg/Lys-specific GalNAC-transferase and the GalNAC β1,4, GlcNAC β1,2 Man α-4 sulfotransferase. J. Biol. Chem. 268, 17096–17102 (1993)

    PubMed  CAS  Google Scholar 

  6. Doll, R.: An overview of the epidemiological evidence linking diet and cancer. Proc. Nutr. Soc. 49, 119–131 (1990)

    PubMed  Article  CAS  Google Scholar 

  7. Dunphy, J.L., Barcham, G.J., Bischot, R., Young, A.R., Nash, A., Meeusen, E.N.T.: Isolation and characterization of a novel eosinophil-specific galectin released into the lungs in response to allergen challenge. J. Biol. Chem. 277, 14916–14924 (2002)

    PubMed  Article  CAS  Google Scholar 

  8. Gray, C.A., Adelson, D.L., Bazer, F.W., Burghardt, R.C., Meeusen, E.N.T., Spencer, T.E.: Discovery and characterization of an epithelial-specific galectin in the endometrium that forms crystals in the trophectoderm. Proc. Natl. Acad. Sci. U. S. A. 10, 7982–7987 (2004)

    Article  Google Scholar 

  9. Gupta, S., Gollapudi, S.: TNF-alpha-induced apoptosis in human naïve and memory CD8+ T cells in aged humans. Exp. Gerontol. 41, 67–77 (2006)

    Article  Google Scholar 

  10. Hagmar, B., Ryd, W., Skomedal, H.: Arabinogalactan blockade of experimental metastases to liver by murine hepatoma. Invasion Metastasis 11, 348–355 (1991)

    PubMed  CAS  Google Scholar 

  11. Hansen, M.B., Nielsen, S.E., Berg, K.: Reexamination and further development of a precise and rapid dye method for measuring cell growth/cell kill. J. Immunol. Methods 119, 203–210 (1989)

    PubMed  Article  CAS  Google Scholar 

  12. Inohara, H., Raz, A.: Effects of natural complex carbohydrate (citrus pectin) on murine melanoma cell properties related to galectin-3 functions. Glycoconj. J. 11, 527–532 (1994)

    PubMed  Article  CAS  Google Scholar 

  13. Kidd, P.: A new approach to metastatic cancer prevention: modified citrus pectin (MCP), a unique pectin that blocks cell surface lectins. Altern. Med. Rev. 1, 4–10 (1996)

    Google Scholar 

  14. Kiyohara, H., Hirano, M., Wen, X.G., Matsumoto, T., Sun, X.B., Yamada, H.: Characterization of an anti-ulcer pectic polysaccharide from leaves of Panax ginseng. Carbohydr. Res. 263, 89–101 (1994)

    PubMed  Article  CAS  Google Scholar 

  15. Kohn, E.C.: Development and prevention of metastasis. Anticancer Res. 13, 2553–2559 (1993)

    PubMed  CAS  Google Scholar 

  16. Konstantinov, K.N., Robbins, B.A., Liu, F.T.: Galectin-3, a beta-galactoside-binding animal lectin, is a marker of anaplastic large-cell lymphoma. Am. J. Pathol. 148, 25–30 (1996)

    PubMed  CAS  Google Scholar 

  17. Nagata, S.: Apoptosis by death factor. Cell 88, 355–365 (1997)

    PubMed  Article  CAS  Google Scholar 

  18. Nangia-Makker, P., Thompson, E., Hogan, C., Ochieng, J., Raz, A.: Induction of tumorigenicity by galectin-3 in a non-tumorigenic human breast carcinoma cell line. Int. J. Oncol. 23, 1079–1087 (1995)

    Google Scholar 

  19. Nangia-Makker, P., Baccarini, S., Raz, A.: Carbohydrate-recognition and angiogenesis. Cancer Metastasis Rev. 19, 51–57 (2000)

    PubMed  Article  CAS  Google Scholar 

  20. Nangia-Makker, P., Hogan, V., Honjo, Y., Sarvis, R., Akahani, S., Pienta, K.J., Raz, A.: Galectin-3 induces endothelial cell morphogenesis and angiogenesis. Am. J. Pathol. 156, 899–909 (2000)

    PubMed  CAS  Google Scholar 

  21. Nangia-Makker, P., Hogan, V., Honjo, Y., Yuichiro, H., 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. Cancer Inst. 94, 1854–1862 (2002)

    PubMed  CAS  Google Scholar 

  22. Nowak, T.P., Haywood, P.L., Barondes, S.H.: Developmentally regulated lectin in embryonic chick muscle and a myogenic cell line. Biochem. Biophys. Res. Commun. 68, 650–657 (1976)

    PubMed  Article  CAS  Google Scholar 

  23. Ochieng, J., Fridman, R., Nagaia Makker, P., Kleiener, D.E., Liotta, L.A., Stetler-Stevenson, W.G., Raz, A.: Galectin-3 is a novel substrate for human matrix metalloproteinases-2 and -9. Biochemistry 33, 14109–14114 (1994)

    PubMed  Article  CAS  Google Scholar 

  24. Ogden, A.T., Nunes, I., Ko, K., Wu, S.J., Hines, C.S., Wang, A.F., Hedge, R.S., Lang, R.A.: GRIFIN: a novel lens-specific protein related to the galectin family. J. Biol. Chem. 273, 28889–28896 (1998)

    PubMed  Article  CAS  Google Scholar 

  25. Olano-Martin, E., Rimbach, G.H., Gibson, G.R., Rastall, R.A.: Pectin and pectic-oligosaccharides induce apoptosis in in vitro human colonic adenocarcinoma cells. Anticancer Res. 23, 341–346 (2003)

    PubMed  CAS  Google Scholar 

  26. Phatak, L., Chang, K.C., Brown, G.: Isolation and characterization of pectin in sugar-beet pulp. J. Food Sci. 53, 830–833 (1988)

    Article  CAS  Google Scholar 

  27. Pienta, K.J., Nailk, H., Akhtar, A., Yamazaki, K., Replogle, T.S., Lehr, J., Donat, T.L., Tait, L., Hogan, V., Raz, A.: Inhibition of spontaneous metastasis in a rat prostate cancer model by oral administration of modified citrus pectin. J. Natl. Cancer Inst. 87, 348–353 (1995)

    PubMed  Article  CAS  Google Scholar 

  28. Powell, A.A., LaRue, J.M., Batta, A.K., Martinez, J.D.: Bile acid hydrophobicity is correlated with induction of apoptosis and/or growth arrest in HT 116 cells. Biochem. J. 356, 481–486 (2001)

    PubMed  Article  CAS  Google Scholar 

  29. Rao, P., Pattabiraman, T.N.: Reevaluation of the phenol-sulfuric acid reaction for the estimation of hexoses and pentoses. Anal. Biochem. 181, 18–22 (1989)

    PubMed  Article  CAS  Google Scholar 

  30. Rabinovich, G.A.: Galectins: an evolutionarily conserved family of animal lectins with multifunctional properties; a trip from the gene to clinical therapy. Cell Death Differ. 6, 711–721 (1999)

    PubMed  Article  CAS  Google Scholar 

  31. Rajeshwari, N., Shylaja, M.D., Krishnappa, M., Shetty, H.S., Mortensen, C.N., Mathur, S.B.: Development of ELISA for the detection of Ralstonia solanacearum in tomato: its application in seed health testing. World J. Micro. Biotech. 14, 697–704 (1998)

    Article  Google Scholar 

  32. Raz, A., Lotan, R.: Endogenous galactoside-binding lectins: a new class of functional tumor cell surface molecules related to metastasis. Cancer Metastasis Rev. 6, 433–452 (1987)

    PubMed  Article  CAS  Google Scholar 

  33. Raju, T.S., Jagadish, R.L., Anjaneyalu, Y.V.: Characterization of EDTA-soluble polysaccharides from the scape of Musa paradisiaca (banana). Biotechnol. Appl. Biochem. 33, 53–59 (2001)

    PubMed  Article  CAS  Google Scholar 

  34. Song, Y.K., Billiar, T.R., Lee, Y.J.: Role of galectin-3 in breast cancer metastasis: involvement of nitric oxide. Am. J. Pathol. 160, 1069–1075 (2002)

    PubMed  CAS  Google Scholar 

  35. Stierstorfer, B., Kaltner, H., Neumuller, C., Sinowatz, F., Gabius, H.J.: Temporal and spatial regulation of expression of two galectins during kidney development of the chicken. Histochem. J. 32, 325–336 (2000)

    PubMed  Article  CAS  Google Scholar 

  36. Takenaka, Y., Fukumori, T., Raz, A.: Galectin-3 and metastasis. Glycoconj. J. 19, 543–549 (2004)

    PubMed  Article  Google Scholar 

  37. Tharanathan, R.N., Changala Reddy, G., Muralikrishna, G., Susheelamma, N.S., Ramadas Bhat, U.: Structure of a galactoarabinan-rich pectic polysaccharide of native and fermented blackgram (Phaseolus mungo). Carbohydr. Polym. 23, 121–127 (1994)

    Article  CAS  Google Scholar 

  38. Uhlenbruck, G., Beuth, J., Oette, K., Roszkowski, W., Ko, H.L., Pulverer, G.: Prevention of experimental liver metastasis by arabinogalactan. Naturwissenschaften 73, 626–627 (1986)

    PubMed  Article  CAS  Google Scholar 

  39. Chanana, V., Majumdar, S., Rishi, P.: Involvement of caspase-3, lipid peroxidation and TNF-alpha in causing apoptosis of macrophages by coordinately expressed Salmonella phenotype under stress conditions. Mol. Immunol. 44, 1551–1558 (2007)

    PubMed  Article  CAS  Google Scholar 

  40. Wong, C.K., Leung, K.N., Fung, K.P.: Immunomodulatory and anti-tumor polysaccharides from medicinal plants. J. Int. Med. Res. 22, 299–312 (1994)

    PubMed  CAS  Google Scholar 

  41. Zhu, W.Q., Ochieng, J.: Rapid release of galectin-3 from breast carcinoma cells by fetuin. Cancer Res. 61, 1869–1873 (2001)

    PubMed  CAS  Google Scholar 

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Acknowledgement

Authors thank Dr. V. Prakash, Director, CFTRI, for his keen interest in the work and encouragement. Authors are also thankful to Dr. S.G. Bhat, Head, Department of Biochemistry and Nutrition and Dr. H.P. Ramesh, Head, Cell Culture Facility for their help. SMD thank Department of Biotechnology, New Delhi, India and Department of Science and Technology, New Delhi, India for financial assistance.

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Correspondence to Shylaja M. Dharmesh.

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Sathisha, U.V., Jayaram, S., Harish Nayaka, M.A. et al. Inhibition of galectin-3 mediated cellular interactions by pectic polysaccharides from dietary sources. Glycoconj J 24, 497–507 (2007). https://doi.org/10.1007/s10719-007-9042-3

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  • DOI: https://doi.org/10.1007/s10719-007-9042-3

Keywords

  • Galectin-3
  • Pectic polysaccharide
  • Hemagglutination
  • Anti metastatic activity
  • Arabinogalactan
  • Modified pectic polysaccharide