Skip to main content

Advertisement

Log in

Antitumor activity of N-acetyl-d-glucosamine-substituted glycoconjugates and combined therapy with keyhole limpet hemocyanin in B16F10 mouse melanoma model

  • Published:
Folia Microbiologica Aims and scope Submit manuscript

Abstract

N-Acetyl-d-glucosamine-substituted glycoconjugates (GCJs) with the polyamidoamine (GN8P) or calix[4]arene (GN4C) scaffold represent ligands for NKR-P1 molecule and induce NK cell-mediated cytotoxicity in vitro. The in vivo effect of these GCJs on mouse melanoma model was determined when administered either alone or in combination with non-specific immunostimulator keyhole limpet hemocyanin (KLH). All types of treatment significantly reduced the tumor growth on day 23, while GN4C as well as KLH were effective continuously (from day 14). The GN4C also induced the longest mean survival time (46.3 ± 11.1 d), followed by KLH+GN4C (36.4 ± 12.1), KLH (35.6 ± 6.5), KLH+GN8P (35.6 ± 6.7), and GN8P (32.4 ± 7.0), compared to controls (29.8 ± 3.6). The B16F10 specific cytotoxicity of peripheral blood cells was significantly elevated by both KLH and GN8P, whereas not by GN4C. KLH increased the effect of the GN4C, but did not influence that of GN8P. GN4C was proved to exert anticancer activity in mouse melanoma model. The combination of KLH with GCJs did not generate synergism.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

Abbreviations

CTL:

cytotoxic T lymphocyte

EGFR1:

epithelial growth factor receptor 1

GlcNAc:

N-acetyl-d-glucosamine

GCJ(s):

glycoconjugate(s)

GN4C:

N-acetyl-d-glucosamine-substituted calix[4]arene

GN8P:

N-acetyl-d-glucosamine-substituted polyamidoamine dendrimer

IFN:

interferon

IL:

interleukin

KLH:

keyhole limpet hemocyanin

NK:

natural killer

NKR-P1:

natural killer cell receptor protein 1

NKT:

natural killer T cell

PBCs:

peripheral blood cells

PBMCs:

peripheral blood mononuclear cells

References

  • Benson V., Grobarova V., Richter J., Fiserova A.: Glycosylation regulates NK cell-mediated effector function through PI3K pathway. Internat.Immunol., in press (2010).

  • Bezouska K.: Design, functional evaluation and biomedical applications of carbohydrate dendrimers (glycodendrimers). J.Biotechnol.90, 269–290 (2002).

    CAS  PubMed  Google Scholar 

  • Bezouska K., Yuen C.T., O’Brien J., Childs R.A., Chai W., Lawson A.M., Drbal K., Fiserova A., Pospisil M., Feizi T.: Oligosaccharide ligands for NKR-P1 protein activate NK cells and cytotoxicity. Nature372, 150–157 (1994).

    Article  CAS  PubMed  Google Scholar 

  • Bezouska K., Snajdrova R., Krenek K., Vancurova M., Kadek A., Adamek D., Lhotak P., Kavan D., Hofbauerova K., Man P., Bojarova P., Kren V.: Carboxylated calixarenes bind strongly to CD69 and protect CD69+ killer cells from suicidal cell death induced by tumor cell surface ligands. Bioorg.Med.Chem.18, 1434–1440 (2010).

    Article  CAS  PubMed  Google Scholar 

  • Fiserova A., Starec M., Kuldova M., Kovaru H., Pav M., Vannucci L., Pospisil M.: Effects of D2-dopamine and α-adrenoreceptor antagonists in stress induced changes on immune responsiveness of mice. J.Neuroimmunol.130, 55–65 (2002).

    Article  CAS  PubMed  Google Scholar 

  • Harris J.R., Markl J.: Keyhole limpet hemocyanin (KLH): a biomedical review. Micron30, 597–623 (1999).

    Article  CAS  PubMed  Google Scholar 

  • Hulikova K., Benson A., Svoboda J., Sima P., Fiserova A.: N-Acetyl-d-glucosamine-coated polyamidoamine dendrimer modulates antibody formation via natural killer cell activation. Internat.Immunopharmacol.9, 792–799 (2009).

    Article  CAS  Google Scholar 

  • Jurincic-Winkler C.D., Metz K.A., Beuth J., Klippel K.F.: Keyhole limpet hemocyanin for carcinoma in situ of the bladder: a longterm follow-up study. Eur.Urol.37, 45–49 (2000).

    Article  CAS  PubMed  Google Scholar 

  • Krenek K., Kuldova M., Hulikova K., Stibor I., Lhotak P., Dudic M., Budka J., Pelantova H., Bezouska K., Fiserova A., Kren V.: N-Acetyl-d-glucosamine substituted calix[4]arenes as stimulators of NK cell-mediated antitumor immune response. Carbohydr.Res.342, 1781–1792 (2007).

    Article  CAS  PubMed  Google Scholar 

  • Kuldová M., Svoboda J., Kovářů F., Vannucci L., Kovářů H., Fišerová A.: NK cell-mediated cytotoxicity modulation by A2 adenosine receptor agonist in different mammalian species. Folia Microbiol.54, 364–368 (2009).

    Article  Google Scholar 

  • Lanier L.L.: NK cell recognition. Ann.Rev.Immunol.23, 225–274 (2005).

    Article  CAS  Google Scholar 

  • Lindhorst T.K., Kieburg C.: Glycocoating of oligovalent amines: synthesis of thiourea-bridged cluster glycosides from glycosyl isothiocyanates. Agnew.Chem. Internat.Ed.Engl.35, 1953–1956 (1996).

    Article  CAS  Google Scholar 

  • Lindhorst T.K.: Artificial multivalent sugar ligands to understand and manipulate carbohydrate-protein interactions. Host-Guest Chem.218, 201–235 (2002).

    Article  CAS  Google Scholar 

  • Mcfadden D.W., Riggs D.R., Jackson B.J., Vona-Davis L.: Keyhole limpet hemocyanin, a novel immune stimulant with promising anticancer activity in Barrett’s oesophageal adenocarcinoma. Am.J.Surg.186, 552–555 (2003).

    Article  CAS  PubMed  Google Scholar 

  • Mcfadden D.W., Riggs D.R., Jackson B.J., Ng A., Cunningham C.: Keyhole limpet hemocyanin potentiates standard immunotherapy for melanoma. Am.J.Surg.193, 284–287 (2007).

    Article  CAS  PubMed  Google Scholar 

  • Pospisil M., Vannucci L., Fiserova A., Sadalapure K., Krausova K., Horvath O., Kren V., Mosca F., Lindhorst T.K., Bezouska K.: Glycodendrimeric ligands of C-type lectin receptors as therapeutic agents in experimental cancer. Adv.Exp Med.Biol.495, 343–348 (2001).

    CAS  PubMed  Google Scholar 

  • Riggs D.R., Jackson B.S., Vona-Davis L., Mcfadden D.: In vitro anticancer effects of a novel immunostimulant: keyhole limpet hemocyanin. J.Surg.Res.108, 279–284 (2002)

    Article  CAS  PubMed  Google Scholar 

  • Rizvi I., Riggs D.R., Jakson B.J., Mcfadden D.W.: Keyhole limpet hemocyanin: an effective adjunct against melanoma in vivo. Am.J.Surg.194, 628–632 (2007).

    Article  CAS  PubMed  Google Scholar 

  • Vannucci L., Fiserova A., Sadalapure K., Lindhorst T.K., Kuldova M., Rossman P., Horvath O., Kren V., Krist P., Bezouska K., Luptovcova M., Mosca F., Pospisil M.: Effects of N-acetyl-glucosamine-coated glycodendrimers as biological modulators in the B16F10 melanoma model in vivo. Internat.J.Oncol.23, 285–296 (2003).

    CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to A. Fišerová.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Hulíková, K., Grobárová, V., Křivohlavá, R. et al. Antitumor activity of N-acetyl-d-glucosamine-substituted glycoconjugates and combined therapy with keyhole limpet hemocyanin in B16F10 mouse melanoma model. Folia Microbiol 55, 528–532 (2010). https://doi.org/10.1007/s12223-010-0087-5

Download citation

  • Received:

  • Revised:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12223-010-0087-5

Keywords

Navigation