Exogenous Natural Glycoprotein Multiple Mechanisms of Anti-tumor Activity

  • Yuan, Hong-Liang (Harbin Commercial University Life Science and Environmental Science Research Center) ;
  • Liu, Xiao-Lei (College of Pharmacy, Harbin University of Commerce) ;
  • Dai, Qi-Chang (Harbin Commercial University Life Science and Environmental Science Research Center) ;
  • Song, Hui (Harbin Commercial University Life Science and Environmental Science Research Center)
  • Published : 2015.03.09


Natural glycoproteins can induce apoptosis of tumor cells and exert anti-tumor activity by immunomodulatory functions, cytotoxic and anti-inflammation effects, and inhibition of endothelial growth factor. Given their prospects as novel agents, sources of natural antitumor glycoproteins have attracted attention and new research directions in glycoprotein biology are gradually shifting to the direction of cancer treatment and prevention of neoplastic disease. In this review, we summarize the latest findings with regard to the tumor suppressor signature of glycoproteins and underlying regulatory mechanisms.


Glycoprotein;antitumor;immunomodulatory;cytotoxicity;antiinflammation;endothelial growth factor


Supported by : Commerce Natural Science Foundation


  1. Andrews P, Zhao X, Allen J, et al (2008). A comparison of the effectiveness of selected non-steroidal anti-inflammatory drugs and their derivatives against cancer cells in vitro. Cancer Chemother Pharmacol, 61, 203-14
  2. Barik S, Bhuniya A, Banerjee S, et al (2013). Neem leaf glycoprotein is superior than Cisplatin and Sunitinib malate in restricting melanoma growth by normalization of tumor microenvironment. Int Immunopharmacol, 17, 42-9.
  3. Banerjee S, Ghosh T, Barik S, et al (2014). Neem leaf glycoprotein prophylaxis transduces immune dependent stop signal for tumor angiogenic switch within tumor microenvironment. PLoS One, 9, 110040.
  4. Bose A, Chakraborty K, Sarkar K, et al (2009). Neem leaf glycoprotein directs T-bet-associated type 1 immune commitment. Hum Immunol, 70, 6-15.
  5. Chiu CH, Peng CC, Ker YB, et al (2014). Physicochemical characteristics and anti-inflammatory activities of antrodan, a novel glycoprotein isolated from Antrodia cinnamomea mycelia. Molecules, 19, 22-40.
  6. Dai L, Wang H, Chen Y (2000). The immune-enhancing effect of PcG-A-a glycoprotein isolated from dried root of pulsatilla chinensis (bunge) regel. Chin J Biochemical Pharmaceutics, 21, 230-1.
  7. Das A, Barik S, Banerjee S, et al (2014). A monoclonal antibody against neem leaf glycoprotein recognizes carcinoembryonic antigen (CEA) and restricts CEA expressing tumor growth. J Immunother, 37, 394-406.
  8. Deepak AV, Salimath BP (2006). Antiangiogenic and proapoptotic activity of a novel glycoprotein from U. indica is mediated by NF-kB and caspase activated DNase in ascites tumor model. Biochimie, 88, 297-307.
  9. Feng Y, Gross S, Wolf NM, et al (2014). Nucleoside diphosphate kinase B regulates angiogenesis through modulation of vascular endothelial growth factor receptor type 2 and endothelial adherens junction proteins. Arterioscler Thromb Vasc Biol, 34, 2292-300.
  10. Goswami KK, Barik S, Sarkar M, et al (2014). Targeting STAT3 phosphorylation by neem leaf glycoprotein prevents immune evasion exerted by supraglottic laryngeal tumor induced M2 macrophages. Mol Immunol, 59, 119-27.
  11. Go H, Hwang HJ, Nam TJ (2010). A glycoprotein from Laminaria japonica induces apoptosis in HT-29 colon cancer cells. Toxicol in Vitro, 24, 1546-53.
  12. Grigorian A, Torossian S, Demetriou M (2009). T-cell growth, cell surface organization, and the galectin glycoprotein lattice. Immunol Rev, 230, 232-46.
  13. Gupta S, Zhang D, Yi J, et al (2004). Anticancer activities of Oldenlandia diffusa. J Herb Pharmacother, 4, 21-33.
  14. Gu QQ, Fang YC, Xin XL, et al (2001). Effects of glycoprotein from Chlamys farreri on tumor growth and immune function in mice. Acta Nut Sin, 23, 200-2.
  15. Han YL, Xie K (2006). The glycoprotein group extracted and purified from Eupolyphaga sinensis walker inhibits the growth of tumor cell in vitro. J Shantou Univ (Nat Sci), 21, 46-50.
  16. Huang Y, Snuderl M, Jain RK (2011), Polarization of tumor associated macrophages: a novel strategy for vascular normalization and antitumor immunity. Cancer Cell, 19, 1-2.
  17. Hanahan D, Weinberg RA (2011). Hallmarks of cancer: the next generation. Cell, 144, 646-74.
  18. Heo KS, Lim KT (2005). Glycoprotein isolated from Solanum nigrum L. modulates the apoptotic-related signals in 12-O-tetradecanoylphorbol 13-acetate-stimulated MCF-7 cells. J Med Food, 8, 69-77.
  19. Kumar VB, Binu S, Soumya SJ, et al (2014). Regulation of vascular endothelial growth factor by metabolic context of the cell. Glycoconj J, 31, 427-34.
  20. Lee J, Lim KT (2012). Inhibitory effect of Styrax Japonica Siebold, Zuccarini glycoprotein (38kDa) on interleukin-$1{\beta}$ and induction proteins in chromium (VI)-treated BNL CL.2 cells. Mol Cell Biochem, 367, 103-11.
  21. Lee J, Lim KT (2012). SJSZ glycoprotein (38kDa) prevents thymus atrophy and enhances expression of IL-2 and IL-12 in diethylnitrosamine-induced hepatocarcinogenesis. Int Immunopharmacol, 13, 362-9.
  22. Lee J, Lee SJ, Lim KT (2014). ZPDC glycoprotein (24kDa) induces apoptosis and enhances activity of NK cells in N-nitrosodiethylamine-injected Balb/c. Cell Immunol, 289, 1-6.
  23. Lee SJ, Oh PS, Ko JH, et al (2004). A 150-kDa glycoprotein isolated from Solanum nigrum L. has cytotoxic and apoptotic effects by inhibiting the effects of protein kinase C alpha, nuclear factor-kappa B and inducible nitric oxide in HCT-116 cells. Cancer Chemother Pharmacol, 54, 562-72.
  24. Liang JH, Wong KP (2000). The characterization of angiogenesis inhibitor from shark cartilage. Adv Exp Med Biol, 476, 209-23.
  25. Liu P, Tao WY, Sun ZH, et al (2001). The antitumor effect and mechanism of active glycoprotein MTSGS1 from tricholoma matsutake mycelium. Pharm Biotechnol, 8, 284-7
  26. Lin JY, Tserng KY, Chen CC (1970). Abrin and ricin: new antitumor substances. Nature, 227, 292-3.
  27. Lee J, Lim KT (2011), Inhibitory effect of plant-originated glycoprotein (27kDa) on expression of matrix metalloproteinase-9 in cadmium chloride-induced BNL CL.2 cells. J Trace Elem Med Biol, 25, 239-46.
  28. Mariana CC. Silva, Claudia AA. de Paula, et al (2014). Bauhinia forficata lectin (BfL) induces cell death and inhibits integrinmediated adhesion on MCF7 human breast cancer cells. Biochim Biophys Acta, 1840, 2262-71.
  29. Mantovani A, Allavena P, Sica A, Balkwill F (2008). Cancerrelated inflammation. Nature, 454, 436-44.
  30. Nie SP, Xie MY, Fu ZH, et al (2008). Study on the purification and chemical compositions of tea glycoprotein. Carbohyd Polym, 71, 626-33.
  31. Nie SP, Xie MY, Zhou P, et al (2007). In vitro antioxidative and anticancer activities of tea glycoprotein in green tea. Eur Food Res Technol, 224, 437-42.
  32. Pattrick G, Richardson SW, Casolaro M, et al (2001). Poly (amdoamine) mediated intracytoplasmic delivery of ricin A-chain and gelonin. J Control Release, 77, 225-33.
  33. Pandurangan AK, Dharmalingam P, Ananda Sadagopan SK, et al (2012). Effect of luteolin on the levels of glycoproteins during azoxymethane-induced colon carcinogenesis in mice. Asian Pac J Cancer Prev, 13, 1569-73.
  34. Qian JY, Liu D, Sun HC (2005). Study on functional properties of sweet potato glycoprotein-an in vitro antitumor and ames tests. Food Sci, 26, 216-8 (in Chinese).
  35. Roy S, Barik S, Banerjee S, et al (2013). Neem leaf glycoprotein overcomes indoleamine 2,3 dioxygenase mediated tolerance in dendritic cells by attenuating hyperactive regulatory T cells in cervical cancer stage IIIB patients. Hum Immunol, 74, 1015-23.
  36. Sandra D, Eli P, Michael K, et al (2010). Cancer and inflammation: promise for biological therapy. J Immunother, 33, 335-51.
  37. Sujit K. Bhutia, Tapas K. Maiti (2011). Chapter 49-Crabs Eye (Abrus precatorius) Seed and Its Immunomodulatory and Antitumor Properties. Nuts and Seeds in Health and Disease Prevention, 409-15.
  38. Suyalatu, Huang FL, Zhang JX, et al (2010). Research Progress of Ricin, J Inner Mongolia Univ Nat, 25, 419-22.
  39. Takahashi M, Kuroki Y, Ohtsubo K, et al (2009). Core fucose and bisecting GlcNAc, the direct modifiers of the N-glycan core: their functions and target proteins. Carbohydr Res, 344, 1387-90.
  40. Tsai PF, Ma CY, Wu JS (2013). A novel glycoprotein from mushroom Hypsizygus marmoreus (Peck) Bigelow with growth inhibitory effect against human leukaemic U937 cells. Food Chemistry, 141, 1252-8.
  41. Wang HY, Wu LJ, Yuan Y, et al (2012). Advances on the antitumor effects of glycoprotein and its mechanism. Ningxia J Agri Fores, 53, 119-21.
  42. Wei YQ, Xu HY, Xu ZH, et al (2005). Inhibition effect of glycoprotein MTS03 from the submerged mycelia of tricholoma madsutake on proliferation in MCF-7 cells in vitro. Chin Pharm J, 40, 1545-8.
  43. Wu PK, Chi Shing Tai W, Liang ZT, et al (2009). Oleanolic acid isolated from Oldenlandia diffusa exhibits a unique growth inhibitory effect against ras-transformed fibroblasts. Life Sci, 85, 113-21.
  44. Yang Q, Zhong JY, Li S, et al (2011). Effects of seaweed pigment glycoprotein on caspase-3 and bax protein expression of hepatoma cells. Progress Modern Biomedicine, 11, 1771-4.
  45. Yin LH, Xiong SD, Ye AF, et al (2010). Effect of momordin in inhibiting proliferation and inducing apoptosis of multidrugresistant K562/A02 cells and its molecular mechanism. Tumor, 30, 288-91.
  46. Zhai Q, Li X, Yang Y, Yu L, et al (2014). Antitumor activity of a polysaccharide fraction from Laminaria japonica on U14 cervical carcinoma-bearing mice. Tumour Biol, 35, 117-22.
  47. Zhang LS, Liu SL (2006). Isolation of anticancer proteins from lorathlorace and part property studying. Nat Prod Res Dev, 18, 43-6.
  48. Zou Z, Yi Y, Wu H. Wu J, Liaw C, Lee K (2003). Intercedensides A-C, three new cytotoxic triterpene glycosides from the sea cucumber Mensamaria intercedens Lampert. J Nat Prod, 66, 1055-60.