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Immunomodulatory and anti-metastatic activities of polysaccharide isolated from red cabbage

적양배추에서 분리한 다당의 면역 및 항전이 활성

  • Received : 2019.04.17
  • Accepted : 2019.05.27
  • Published : 2019.06.30

Abstract

In this study, we examined the immunostimulating characteristics of a hot water extract (RCW) and crude polysaccharides (RCP) of red cabbage. RCW and RCP did not show any cytotoxicity in B16BL6 cells and macrophages. Although the sugar compositions of RCW and RCP were similar, the uronic acid content of RCP was higher than that of RCW RCP significantly increased the production of various cytokines and NO, whereas RCW did not affect the production of cytokines and NO. In an ex vivo assay of natural killer (NK) cell activity, intravenous (i.v.) administration of RCP significantly augmented NK cytotoxicity against Yac-1 tumor cells at 3 days after RCP treatment. In an experimental lung metastasis model using B16BL6 melanoma cells, i.v. administration of RCP at a dose of $1,000{\mu}g$ per mouse significantly inhibited 47.3% of lung metastasis. These results suggest that crude polysaccharide isolated from red cabbage is a promising food ingredient for the prevention of tumor metastasis.

Keywords

red cabbage;polysaccharide;macrophage;anti-tumor;NK cells

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Fig. 1. Isolation of water extract and crude polysaccharides from red cabbage and their HPLC chromatograms.

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Fig. 2. Cytotoxic effect of RCW and RCP isolated from the red cabbage on macrophage cells (A) and B16BL6 melanoma cell lines (B) in vitro.

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Fig. 3. Effect of RCW and RCP on the secretion of cytokines (IL-6, IL-12 and TNF-α) and nitric oxide (NO) in murine peritoneal macrophages.

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Fig. 4. Effect of RCP on cytolytic activity of natural killer (NK) cells ex vivo.

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Fig. 5. Inhibitory effect of RCP from red cabbage on lung metastasis produced by i.v. inoculation of B16BL6 melanoma cells.

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Fig. 6. Single radial gel diffusion (A) and reactivity (B) between β-glucosyl Yariv reagent and polysaccharide fractions isolated from red cabbage.

Table 1. Analytical conditions of samples by HPLC and GC

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Table 2. Chemical properties of RCW and RCP isolated from red cabbage

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References

  1. Vivier E, Biron CA. A pathogen receptor on natural killer cells. Science 296: 1248-1249 (2002)
  2. Walzer T, Dalod M, Vivier E, Zitvogel L. Natural killer cell-dendritic cell crosstalk in the initiation of immune responses. Expert Opin. Biol. Ther. 5: 49-59 (2005)
  3. Wiczkowski W, Szawara-Nowak D, Topolska J. Red cabbage anthocyanins: Profile, isolation, identification, and antioxidant activity. Food Res. Int. 51: 303-309 (2013)
  4. Wigginton JM, Kuhns DB, Back TC, Brunda MJ, Wiltrout RH, Cox GW. Interleukin 12 primes macrophages for nitric oxide production in vivo and restores depressed nitric oxide production by macrophages from tumor-bearing mice: implications for the antitumor activity of interleukin 12 and/or interleukin 2. Cancer Res. 56: 1131-1136 (1996)
  5. Zhang Y, Talalay P. Anticarcinogenic activities of organic isothiocyanates: chemistry and mechanisms. Cancer Res. 54: 1976-1981 (1994)
  6. Beutler B. Innate immunity: An overview. Mol. Immunol. 40: 845-859 (2004)
  7. Pennini ME, Perkins DJ, Salazar AM, Lipsky M, Vogel SN. Complete dependence on IRAK4 kinase activity in TLR2, but not TLR4, signaling pathways underlies decreased cytokine production and increased susceptibility to Streptococcus pneumoniae infection in IRAK4 kinase-inactive mice. J. Immunol. 190: 307-316 (2013)
  8. Raulet DH. Interplay of natural killer cells and their receptors with the adaptive immune response. Nat. Immunol. 5: 996-1002. (2004)
  9. Schepetkin IA, Faulkner CL, Nelson-Overton LK, Wiley JA, Quinn MT. Macrophage immunomodulatory activity of polysaccharides isolated from Juniperus scopolorum. Int. Immunopharmacol. 5: 1783-1799 (2005)
  10. Schepetkin IA, Quinn MT. Botanical polysaccharides: Macrophage immunomodulation and therapeutic potential. Int. Immunopharmacol. 6: 317-333 (2006)
  11. Smyth MJ, Taniguchi M, Street SE. The anti-tumor activity of IL-12: mechanisms of innate immunity that are model and dose dependent. J. Immunol. 165: 2665-2670 (2000)
  12. Statistics Korea. Annual report on the causes of death statistics. 11-1240000-000028-10. 1-75 (2017)
  13. Tominaga H, Ishiyama M, Ohseto F, Sasamoto K, Hamamoto T, Suzuki K, Watanabe M. A water-soluble tetrazolium salt useful for colorimetric cell viability assay. Anal. Commun. 36: 47-50 (1999)
  14. Trinchieri G. Interleukin-12 and its role in the generation of Th1 cells. Immunol. Today 14: 335-338 (1993) https://doi.org/10.1016/0167-5699(93)90230-I
  15. Trinchieri G. Interleukin-12: A cytokine produced by antigen-presenting cells with immunoregulatory functions in the generation of T-helper cells type 1 and cytotoxic lymphocytes. Blood 84: 4008-4027 (1994)
  16. van Holst GJ, Clarke AE. Quantification of arabinogalactan-protein in plant extracts by single radial gel diffusion. Anal. Biochem. 148: 446-450 (1985)
  17. Kobayashi M, Fitz L, Ryan M, Hewick RM, Clark SC, Chan S, Loudon R, Sharman F, Trinchieri G. Identification and purification of natural killer cell stimulatory factor (NKSF), a cytokine with multiple biologic effects on human lymphocytes. J. Exp. Med. 170: 827-845 (1989) https://doi.org/10.1084/jem.170.3.827
  18. Lee EH, Park HR, Shin MS, Cho SY, Choi HJ, Shin KS. Antitumor metastasis activity of pectic polysaccharide purified from the peels of Korean Citrus Hallabong. Carbohydr. Polym. 111: 72-79 (2014) https://doi.org/10.1016/j.carbpol.2014.04.073
  19. Li Q, Zhang F, Chen G, Chen Y, Zhang W, Mao G, Zhao T, Zhang M, Yang L, Wu X. Purification, characterization and immunomodulatory activity of a novel polysaccharide from Grifola frondosa. Int. J. Biol. Macromol. 111: 1293-1303 (2018)
  20. Lolis E, Bucala R. Therapeutic approaches to innate immunity: Severe sepsis and septic shock. Nat. Rev. Drug Discov. 2: 635-645 (2003)
  21. Manetti R, Parronchi P, Giudizi MG, Piccinni MP, Maggi E, Trinchieri G, Romagnani S. Natural killer cell stimulatory factor (interleukin 12 [IL-12]) induces T helper type 1 (Th1)-specific immune responses and inhibits the development of IL-4-producing Th cells. J. Exp. Med. 177: 1199-1204 (1993)
  22. Moretta L, Moretta A. Unravelling natural killer cell function: Triggering and inhibitory human NK receptors. EMBO J. 23: 255-259 (2004)
  23. O'Neill M, Albersheim P, Darvill A. The pectic polysaccharides of primary cell walls. pp. 415-441. In: Methods in Plant Biochemistry. Bryant JA. Carbohydrates, Academic, London, England (1990)
  24. Park SO, Kim JM. Functional food for immune regulation-beta-glucan. Food Science and Industry 45: 39-47 (2012)
  25. Gruchalla RS, Jones J. Combating high-priority biological agents: what to do with drug-allergic patients and those for whom vaccination is contraindicated?. J. Allergy Clin. Immunol. 112: 675-682 (2003)
  26. Hackett CJ. Innate immune activation as a broad-spectrum biodefense strategy: Prospects and research challenges. J. Allergy Clin. Immunol. 112: 686-694 (2003)
  27. Hwang YC, Shin KS. Characterization of immuno-stimulating polysaccharides isolated from Korean persimmon vinegar. Korean J. Food Sci. Technol. 4: 220-227 (2008)
  28. Jones TM, Albersheim P. A gas chromatographic method for the determination of aldose and uronic acid constituents of plant cell wall polysaccharides. Plant Physiol. 49: 926-936 (1972)
  29. Karkhanis YD, Zeltner JY, Jackson JJ, Carlo DJ. A new and improved microassay to determine 2-keto-3-deoxyoctonate in lipopolysaccharide of gram-negative bacteria. Anal. Biochem. 85: 595-601 (1978)
  30. Kawai T, Akira S. The role of pattern-recognition receptors in innate immunity: Update on Toll-like receptors. Nat. Immunol. 11: 373 (2010)
  31. Kim HS. Natural Killer Cell and Cancer Immunotherapy. Hanyang Med. Rev. 33: 59-64 (2013) https://doi.org/10.7599/hmr.2013.33.1.59
  32. Kim HW, Shin MS, Lee SJ, Park HR, Jee HS, Yoon TJ, Shin KS. Signaling pathways associated with macrophage-activating polysaccharides purified from fermented barley. Int. J. Biol. Macromol. 131: 1084-1091 (2019)
  33. Knutson KL, Disis ML. Tumor antigen-specific T helper cells in cancer immunity and immunotherapy. Cancer Immun. Immunotherapy 54: 721-728 (2005)
  34. Carpita NC, Gibeaut DM. Structural models of primary cell walls in flowering plants: consistency of molecular structure with the physical properties of the walls during growth. Plant J. 3: 1-30 (1993)
  35. Carpita N, McCann M. The cell wall. pp. 52-108. In: Biochemistry and Molecular Biology of Plants. Buchanan BB (ed). American Society of Plant Physiologists, Maryland, Md, USA (2000)
  36. Chen X, Hu ZP, Yang XX, Huang M, Gao Y, Tang W, Chan SY, Dai X, Ye J, Ho PCL, Duan W, Yang HY, Zhu YZ, Zhou SF. Monitoring of immune responses to a herbal immuno-modulator in patients with advanced colorectal cancer. Int. Immunopharmacol. 6: 499-508 (2006)
  37. Clarke AE, Anderson RL, Stone BA. Form and function of arabinogalactans and arabinogalactan-proteins. Phytochemistry 18: 521-540 (1979)
  38. Diwanay S, Chitre D, Patwardhan B. Immunoprotection by botanical drugs in cancer chemotherapy. J. Ethnopharmacol. 90: 49-55 (2004)
  39. Dubois M, Gilles KA, Hamilton JK, Rebers PA, Smith F. Colorimetric method for determination of sugars and related substances. Anal. Chem. 28: 350-356 (1956) https://doi.org/10.1021/ac60111a017
  40. Engelsen SB, Cros S, Mackie W, Perez S. A molecular builder for carbohydrates: application to polysaccharides and complex carbohydrates. Biopolymers 39: 417-433 (1996)
  41. Fan Y, Wang W, Song W, Chen H, Teng A, Liu A. Partial characterization and anti-tumor activity of an acidic polysaccharide from Gracilaria lemaneiformis. Carbohydr. Polym. 88: 1313-1318 (2012)
  42. Gately MK, Wolitzky AG, Quinn PM, Chizzonite R. Regulation of human cytolytic lymphocyte responses by interleukin-12. Cellular Immunology 143: 127-142 (1992)
  43. Aspinall GO. Carbohydrate polymers of plant cell wall. pp. 95-115. In: Biogenesis of Plant Cell Wall Polysaccharides. Loewus F (ed). Academic Press, New York, NY, USA (1973)
  44. Blumenkrantz N, Asboe-Hansen G. New method for quantitative determination of uronic acids. Anal. Biochem. 54: 484-489 (1973)
  45. Bradford MM. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal. Biochem. 72: 248-254 (1976)
  46. Brunda MJ, Luistro L, Warrier RR, Wright RB, Hubbard BR, Murphy M, Gately M K. Antitumor and antimetastatic activity of interleukin 12 against murine tumors. J. Exp. Med. 178: 1223-1230 (1993)

Acknowledgement

Supported by : 경기대학교