Skip to main content

Advertisement

SpringerLink
Log in

Sustained mitogenic effect on K562 human chronic myelogenous leukemia cells by dietary lectin, jacalin

  • Short Communication
  • Published:
Glycoconjugate Journal Aims and scope Submit manuscript

Abstract

Dietary lectins have been shown to affect the proliferation of human cancer cell lines. The anti-proliferative effects of lectins from varied sources have been extensively studied and in some cases, the underlying mechanism has been explored. Except for peanut agglutinin (PNA), the mitogenic effects of no other lectins have been studied in detail. In the present study, we have shown that jacalin, lectin purified from jackfruit (Artocarpus integrifolia) seeds act as a mitogen for K562, the Bcr-Abl expressing erythroleukemia cell line (K562) and the effect was found to be dose dependent. K562 cells remained in the proliferative state for a longer period even after the withdrawal of jacalin stimulation, thus jacalin was found to induce sustained mitogenic effect on K562 cells. Further, conditioned media from K562 cells treated with jacalin were observed to have the similar mitogenic effect even in the presence of galactose. Importantly, galactose which is a known ligand for jacalin will interact with functionally active jacalin present in the conditioned media and neutralise its effect. In addition, jacalin treatment also resulted in increased mRNA expression levels of pro-inflammatory cytokines including IL-1β, IL-6 and IFN-γ. Our results indicate that jacalin induces secretion of soluble molecules, which maybe responsible for this observed increased proliferation of K562 cells.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

References

  1. Sharon N.: Lectins: from obscurity into the limelight. Protein Sci. 7, 2042–2048 (1998)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Lis H., Sharon N.: Lectins: carbohydrate-specific proteins that mediate cellular recognition. Chem. Rev. 98, 637–674 (1998)

    Article  CAS  PubMed  Google Scholar 

  3. Pusztai A.: Plant Lectins, Chemistry and Pharmacology of Natural Products Series. Cambridge University Press, Cambridge (1991)

    Google Scholar 

  4. Wang Q., Yu L.G., Campbell B.J., Milton J.D., Rhodes J.M.: Identification of intact peanut lectin in peripheral venous blood. Lancet. 352, 1831–1832 (1998)

    Article  CAS  PubMed  Google Scholar 

  5. Brady P.G., Vannier A.M., Banwell J.G.: Identification of the dietary lectin, wheat germ agglutinin, in human intestinal contents. Gastroenterology. 75, 236–239 (1978)

    CAS  PubMed  Google Scholar 

  6. Ryder S.D., Smith J.A., Rhodes J.M.: Peanut lectin: a mitogen for normal human colonic epithelium and human HT29 colorectal cancer cells. J. Natl. Cancer Inst. 84, 1410–1416 (1992)

    Article  CAS  PubMed  Google Scholar 

  7. Ryder S.D., Parker N., Ecclestone D., Haqqani M.T., Rhodes J.M.: Peanut lectin stimulates proliferation in colonic explants from patients with inflammatory bowel disease and colon polyps. Gastroenterology. 106, 117–124 (1994)

    Article  CAS  PubMed  Google Scholar 

  8. Singh R., Subramanian S., Rhodes J.M., Campbell B.J.: Peanut lectin stimulates proliferation of colon cancer cells by interaction with glycosylated CD44v6 isoforms and consequential activation of c-Met and MAPK: functional implications for disease-associated glycosylation changes. Glycobiology. 16, 594–601 (2006)

    Article  CAS  PubMed  Google Scholar 

  9. Yu L.G., Milton J.D., Fernig D.G., Rhodes J.M.: Opposite effects on human colon cancer cell proliferation of two dietary Thomsen-Friedenreich antigen-binding lectins. J. Cell. Physiol. 186, 282–287 (2001)

    Article  CAS  PubMed  Google Scholar 

  10. Yu L., Fernig D.G., Smith J.A., Milton J.D., Rhodes J.M.: Reversible inhibition of proliferation of epithelial cell lines by Agaricus bisporus (edible mushroom) lectin. Cancer Res. 53, 4627–4632 (1993)

    CAS  PubMed  Google Scholar 

  11. Ryder S.D., Jacyna M.R., Levi A.J., Rizzi P.M., Rhodes J.M.: Peanut ingestion increases rectal proliferation in individuals with mucosal expression of peanut lectin receptor. Gastroenterology. 114, 44–49 (1998)

    Article  CAS  PubMed  Google Scholar 

  12. Ryder S.D., Smith J.A., Rhodes E.G., Parker N., Rhodes J.M.: Proliferative responses of HT29 and Caco2 human colorectal cancer cells to a panel of lectins. Gastroenterology. 106, 85–93 (1994)

    Article  CAS  PubMed  Google Scholar 

  13. Zhao Q., Duckworth C.A., Wang W., Guo X., Barrow H., Pritchard D.M., Rhodes J.M., Yu L.G.: Peanut agglutinin appearance in the blood circulation after peanut ingestion mimics the action of endogenous galectin-3 to promote metastasis by interaction with cancer-associated MUC1. Carcinogenesis. 35, 2815–2821 (2014)

    Article  CAS  PubMed  Google Scholar 

  14. Valentiner U., Fabian S., Schumacher U., Leathem A.J.: The influence of dietary lectins on the cell proliferation of human breast cancer cell lines in vitro. Anticancer Res. 23, 1197–1206 (2003)

    CAS  PubMed  Google Scholar 

  15. Pineau N., Aucouturier P., Brugier J.C., Preud’homme J.L.: Jacalin: a lectin mitogenic for human CD4 T lymphocytes. Clin. Exp. Immunol. 80, 420–425 (1990)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Blasco E., Barra A., Nicolas M., Lecron J.C., Wijdenes J., Preud’homme J.L.: Proliferative response of human CD4+ T lymphocytes stimulated by the lectin jacalin. Eur. J. Immunol. 25, 2010–2018 (1995)

    Article  CAS  PubMed  Google Scholar 

  17. Tamma S.M., Kalyanaraman V.S., Pahwa S., Dominguez P., Modesto R.R.: The lectin jacalin induces phosphorylation of ERK and JNK in CD4+ T cells. J. Leukoc. Biol. 73, 682–688 (2003)

    Article  CAS  PubMed  Google Scholar 

  18. Lafont V., Dornand J., Covassin L., Liautard J.P., Favero J.: The lectin jacalin triggers CD4-mediated lymphocyte signaling by binding CD4 through a protein-protein interaction. J. Leukoc. Biol. 59, 691–696 (1996)

    CAS  PubMed  Google Scholar 

  19. Yu L.G., Andrews N., Weldon M., Gerasimenko O.V., Campbell B.J., Singh R., Grierson I., Petersen O.H., Rhodes J.M.: An Nterminal truncated form of Orp150 is a cytoplasmic ligand for the anti-proliferative mushroom Agaricus bisporus lectin and is required for nuclear localization sequence-dependent nuclearprotein import. J. Biol. Chem. 277, 24538–24545 (2002)

    Article  CAS  PubMed  Google Scholar 

  20. Sahasrabuddhe A.A., Ahmed N., Krishnasastry M.V.: Stress induced phosphorylation of caveolin-1 and p38, and downregulation of EGFr and ERK by the dietary lectin jacalin in two human carcinoma cell lines. Cell Stress Chaperones. 11, 135–147 (2006)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Yu L.G., Fernig D.G., White M.R., Spiller D.G., Appleton P., Evans R.C., Grierson I., Smith J.A., Davies H., Gerasimenko O.V., Petersen O.H., Milton J.D., Rhodes J.M.: Edible mushroom (Agaricus bisporus) lectin, which reversibly inhibits epithelial cell proliferation, blocks nuclear localization sequence-dependent nuclear protein import. J. Biol. Chem. 274, 4890–4899 (1999)

    Article  CAS  PubMed  Google Scholar 

  22. Steelman L.S., Pohnert S.C., Shelton J.G., Franklin R.A., Bertrand F.E., McCubrey J.A.: JAK/STAT, Raf/MEK/ERK, PI3K/Akt and BCR-ABL in cell cycle progression and leukemogenesis. Leukemia. 18, 189–218 (2004)

    Article  CAS  PubMed  Google Scholar 

  23. Bedi A., Zehnbauer B.A., Barber J.P., Jones R.J.: Inhibition of apoptosis by BCR-ABL in chronic myeloid leukemia. Blood. 83, 2038–2044 (1994)

    CAS  PubMed  Google Scholar 

  24. Cortez D., Kadlec L., Pendergast A.M.: Structural and signaling requirements for BCR-ABL-mediated transformation and inhibition of apoptosis. Mol. Cell. Biol. 15, 5531–5541 (1995)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Amarante-Mendes G.P., Naekyung Kim C., Liu L., Huang Y., Perkins C.L., Green D.R., Bhalla K.: Bcr-Abl exerts its antiapoptotic, effect against diverse apoptotic stimuli through blockage of mitochondrial release of cytochrome C and activation of caspase-3. Blood. 91, 1700–1705 (1998)

    CAS  PubMed  Google Scholar 

  26. Gordon M.Y., Dowding C.R., Riley G.P., Goldman J.M., Greaves M.F., et al.: Altered adhesive interactions with marrow stroma of haematopoietic progenitor cells in chronic myeloid leukaemia. Nature. 328, 342–344 (1987)

    Article  CAS  PubMed  Google Scholar 

  27. Chen Y., Peng C., Sullivan C., Li D., Li S.: Critical molecular pathways in cancer stem cells of chronic myeloid leukemia. Leukemia. 24, 1545–1554 (2010)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Agrawal B.B., Goldstein I.J.: Physical and chemical characterization of concanavalin A, the hemagglutinin from jack bean (Canavalia ensiformis). Biochim. Biophys. Acta. 133, 376–379 (1967)

    Article  CAS  PubMed  Google Scholar 

  29. Sastry M.V., Surolia A.: Intrinsic fluorescence studies on saccharide binding to Artocarpus integrifolia lectin. Biosci. Rep. 6, 853–860 (1986)

    Article  CAS  PubMed  Google Scholar 

  30. Sastry M.V., Banarjee P., Patanjali S.R., Swamy M.J., Swarnalatha G.V., Surolia A.: Analysis of saccharide binding to Artocarpus integrifolia lectin reveals specific recognition of T-antigen (β-D-Gal(1—3)D-GalNAc). J. Biol. Chem. 261, 11726–11733 (1986)

    CAS  PubMed  Google Scholar 

  31. Faheina-Martins G.V., da Silveira A.L., Ramos M.V., Marques-Santos L.F., Araujo D.A.: Influence of fetal bovine serum on cytotoxic and genotoxic effects of lectins in MCF-7 cells. J. Biochem. Mol. Toxicol. 25, 290–296 (2011)

    Article  CAS  PubMed  Google Scholar 

  32. Camby I., Janssen T., De Decker R., Petein M., Raviv G., Pasteels J.L., Kiss R., Danguy A.: Lectin-induced alterations on the proliferation of three human prostatic cancer cell lines. In Vitro Cell Dev. Biol. 32, 633–639 (1996)

    Article  CAS  Google Scholar 

  33. Mosmann T.: Rapid colorimetric assay for cellular growth and survival; application to proliferation and cytotoxicity assays. J. Immunol. Methods. 65, 55–63 (1983)

    Article  CAS  PubMed  Google Scholar 

  34. Livak K.J., Schmittgen T.D.: Analysis of relative gene expression data using real-time quantitative PCR and the 2(−Delta Delta C(T)) method. Methods. 25, 402–408 (2001)

    Article  CAS  PubMed  Google Scholar 

  35. Wolf M.F., Ludwig A., Fritz P., Schumacher K.: Increased expression of Thomsen-Friedenreich antigens during tumor progression in breast cancer patients. Tumour Biol. l9, 190–194 (1988)

    Article  Google Scholar 

  36. Campbell B.J., Finnie I.A., Hounsell E.F., Rhodes J.M.: Direct demonstration of increased expression of Thomsen-Friedenreich (TF) antigen in colonic adenocarcinoma and ulcerative colitis mucin and its concealment in normal mucin. J. Clin. Invest. 95, 571–576 (1995)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Inamdar S.R., Savanur M.A., Eligar S.M., Chachadi V.B., Nagre N.N., Chen C., Barclaays M., Ingle A., Mahajan P., Borges A., Shastry P., Kalraiya R.D., Swamy B.M., Rhodes J.M., Yu L.G.: The TF-antigen binding lectin from Sclerotiumrolfsii inhibits growth of human colon cancer cells by inducing apoptosis in vitro and suppresses tumor growth in vivo. Glycobiology. 22, 1227–1235 (2012)

    Article  CAS  PubMed  Google Scholar 

  38. Yagi M., Campos-Neto A., Gollahon K.: Morphological and biochemical changes in a hematopoietic cell line induced by jacalin, a lectin derived from Artocarpus integrifolia. Biochem. Biophys. Res. Commun. 209, 263–270 (1995)

    Article  CAS  PubMed  Google Scholar 

  39. Fadeev R.S., Solovieva M.E., Slyadovskiy D.A., Zkharov S.J., Fadeeva I.S., Senotov A.S., Dolgikh N.V., Golenkov A.K., Akatov V.S.: Cell aggregation increases drug resistance of acute myeloid leukemia cells. Biol. Membr.: Zh. Membr. Klet. Biol. 32, 125–132 (2015)

    CAS  Google Scholar 

  40. Dowling P., Clynes M.: Conditioned media from cell lines: a complementary model to clinical specimens for the discovery of disease-specific biomarkers. Proteomics. 11, 794–804 (2011)

    Article  CAS  PubMed  Google Scholar 

  41. Voronov E., Shouval D.S., Krelin Y., Cagnano E., Benharroch D., Iwakura Y., Dinearello C.A., Apte R.N.: IL-1 is required for tumor invasiveness and angiogenesis. Proc. Natl. Acad. Sci. 100, 2645–2650 (2003)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Pantschenko A.G., Pushkar I., Anderson K.H., Wang Y., Miller L.J., Kurtzman S.H., Barrows G., Kreutzer S.H.: The interleukin-1 family of cytokines and receptors in human breast cancer: implications for tumor progression. Int. J. Oncol. 23, 269–284 (2003)

    CAS  PubMed  Google Scholar 

  43. Li Z., Chen L., Qin Z.: Paradoxical roles of IL-4 in tumor immunity. Cell. Mol. Immunol. l6, 415–422 (2009)

    Article  Google Scholar 

  44. Zaidi M.R., Merlino G.: The two faces of interferon-gamma in cancer. Clin. Cancer Res. 17, 6118–6124 (2011)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Pusztai A., Greer F., Grant G.: Specific uptake of dietary lectins into the systemic circulation of rats. Biochem. Soc. Trans. 17, 481–482 (1989)

    Article  CAS  Google Scholar 

  46. King T.P., Pusztai A., Grant G., Slater D.: Immunogold localization of ingested kidney bean (Phaseolus vulgaris) lectins in epithelial cells of the rat small intestine. Histochem. J. 18, 413–420 (1986)

    Article  CAS  PubMed  Google Scholar 

  47. Kilpatrick D.C., Pusztai A., Grant G., Grahan C., Ewen S.W.B.: Tomato lectin resists digestion in mammalian alimentary canal and binds to intestinal villi without deleterious effects. FEBS Lett. 185, 299–309 (1985)

    Article  CAS  PubMed  Google Scholar 

  48. Higuchi M., Suga M., Iwai K.: Participation of lectin in biological effects of raw winged bean seeds on rats. Agric. Biol. Chem. 47, 1879–1886 (1983)

    CAS  Google Scholar 

  49. Nakata S., Kumura T.: Effects of ingested toxic bean lectins on the gastrointestinal tract in the rat. J. Nutr. 115, 1621–1629 (1985)

    CAS  PubMed  Google Scholar 

Download references

Acknowledgments

The authors thank Prof. JAK Tareen for setting up the School of Life Sciences at BSAU, Prof. S. Hemalatha for her constant support and Ms.M.K. Saranya for technical assistance. L.V. is recipient of a junior research fellowship from B. S. Abdur Rahman University, K.A.K, N.A. and S.J. are Assistant Professors (Senior Grade) at School of Life Sciences, B. S. Abdur Rahman University. Financial assistance was provided by B. S. Abdur Rahman University.

Author information

Authors and Affiliations

  1. School of Life Sciences, B. S. Abdur Rahman University, Vandalur, Chennai, Tamil Nadu, 600048, India

    V. Lavanya, Neesar Ahmed, Md Khurshid Alam Khan & Shazia Jamal

Authors
  1. V. Lavanya
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Neesar Ahmed
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Md Khurshid Alam Khan
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Shazia Jamal
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Shazia Jamal.

Ethics declarations

Conflicts of interest

The authors declare that they have no conflicts of interest.

Ethical approval

This article does not contain any studies with human participants or animals performed by any of the authors.

Electronic supplementary material

ESM 1

(PDF 26 kb)

ESM 2

(PDF 94 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Lavanya, V., Ahmed, N., Khan, M.K.A. et al. Sustained mitogenic effect on K562 human chronic myelogenous leukemia cells by dietary lectin, jacalin. Glycoconj J 33, 877–886 (2016). https://doi.org/10.1007/s10719-016-9725-8

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10719-016-9725-8

Keywords

Search

Navigation