Advertisement

Journal of Natural Medicines

, Volume 72, Issue 3, pp 745–756 | Cite as

Mitogenic activity of Artocarpus lingnanensis lectin and its apoptosis induction in Jurkat T cells

  • Linjie Zeng
  • Lu Li
  • Qiyan Zeng
  • Yong Deng
  • Lijun Yin
  • Liejun Liao
Original Paper

Abstract

Lectins are a class of carbohydrate-binding proteins or glycoproteins and used in the purification and characterization of glycoproteins according to their specificity to carbohydrates. In the present study, the mitogenic activity of Artocarpus lingnanensis lectin (ALL) and its apoptosis induction in Jurkat T cells were explored. MTT assay revealed strong mitogenic potential of ALL. Meanwhile, the anti-cancer activity of ALL was also explored using the human leukemic Jurkat T cell line. ALL exhibited strong binding affinity (97%) to the cell membrane, which could be effectively inhibited by N-acetyl-d-galactosaminide (NAD). ALL induced time- and dose-dependent growth inhibition in Jurkat T cells. ALL could induce morphologic change and increase the hypodiploid cell population with the decreased population of S and G2/M phases. The induction of phosphatidylserine externalization and PARP cleavage further confirmed its apoptosis-inducing activity due to the activation of caspase-8 and -9. The inhibition of caspase-9 but not caspase-8 could rescue ALL-induced apoptotic cells. Further studies showed that ALL enhanced the cleavage of Bid, the release of cytochrome C, the depolarization of mitochondria and the activation of caspase-3. ALL downregulated the expression of Bcl-xl and Bcl-2 without impact on Bax and Bad. In addition, the activation of p38/JNK MAPK signaling pathways was observed to be a requisite for ALL apoptotic activity. In contrast, ALL could not induce apoptosis of normal T cells. These findings present the differential effect of ALL on Jurkat and normal T lymphocytes, suggesting its therapeutic value in leukemia.

Keywords

Lectin Glycoprotein Mitogenic activity Apoptosis Leukemia 

Notes

Acknowledgements

This work was supported by the National Natural Science Foundation of China (no. 81160366) and Guangxi Natural Science Foundation Grant (no. 0832130). The funders had no role in the study design, data collection and analysis, decision to publish or preparation of the manuscript.

Compliance with ethical standards

Conflict of interest

The authors declare that there are no conflicts of interest. The authors alone are responsible for the content and writing of this article.

References

  1. 1.
    Subramanyam S, Smith DF, Clemens JC, Webb MA, Sardesai N, Williams CE (2008) Functional characterization of HFR1, a high-mannose N-glycan-specific wheat lectin induced by Hessian fly larvae. Plant Physiol 147(3):1412–1426CrossRefPubMedPubMedCentralGoogle Scholar
  2. 2.
    Santiago MQ, Leitão CC, Pereira FN Jr, Pinto VR Jr, Osterne VJ, Lossio CF et al (2014) Purification, characterization and partial sequence of a pro-inflammatory lectin from seeds of Canavalia oxyphylla Standl. & L. O. Williams. J Mol Recognit 27(3):117–123CrossRefPubMedGoogle Scholar
  3. 3.
    Hong J, Chen TT, Hu L, Yang J, Hu P, Wang SY (2015) Purification and characterization of a novel lectin from Chinese leek seeds. J Agric Food Chem 63(5):1488–1495CrossRefPubMedGoogle Scholar
  4. 4.
    Dong Q, Sugiura T, Toyohira Y, Yoshida Y, Yanagihara N, Karasaki Y (2011) Stimulation of IFN-c production by garlic lectin in mouse spleen cells: involvement of IL-12 via activation of p38 MAPK and ERK in macrophages. Phytomedicine 18(4):309–316CrossRefPubMedGoogle Scholar
  5. 5.
    Tatsuta T, Hosono M, Sugawara S, Kariya Y, Ogawa Y, Hakomori S, Nitta K (2013) Sialic acid-binding lectin (leczyme) induces caspase-dependent apoptosis-mediated mitochondrial perturbation in Jurkat cells. Int J Oncol 43(5):1402–1412CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Hong CE, Park AK, Lyu SY (2014) Synergistic anticancer effects of lectin and doxorubicin in breast cancer cells. Mol Cell Biochem 94(1–2):225–235CrossRefGoogle Scholar
  7. 7.
    Zhang XS, Wu ZY (1988) Flora reipublicae Popularis Sinicae, vol 23. Beijing Science Press, Beijing, p 53Google Scholar
  8. 8.
    Hakim EH, Asnizar Yurnawilis, Aimi N, Kitajima M, Takayama H (2002) Artoindonesianin P, a new prenylated flavone with cytotoxic activity from Artocarpus lanceifolius. Fitoterapia 73(7–8):668–673CrossRefPubMedGoogle Scholar
  9. 9.
    Fernando MR, Wickramasinghe N, Thabrew MI, Ariyananda PL, Karunanayake EH (1991) Effect of Artocarpus heterophyllus and Asteracanthus longifolia on glucose tolerance in normal human subjects and in maturity-onset diabetic patients. J Ethnopharmacol 31(3):277–282CrossRefPubMedGoogle Scholar
  10. 10.
    Editorial Committee of the Chinese Materia Medica (1999) Chinese materia medica, vol 2. Shanghai Science and Technology Publishing Press, Shanghai, p 467Google Scholar
  11. 11.
    Cui B, Li L, Zeng QY, Lin FQ, Yin L, Liao LJ, Huang M, Wang J (2017) A novel lectin from Artocarpus lingnanensis induces proliferation and Th1/Th2 cytokine secretion through CD45 signaling pathway in human T lymphocytes. J Nat Med 71:409–421CrossRefPubMedGoogle Scholar
  12. 12.
    Brunelle JK, Letai A (2009) Control of mitochondrial apoptosis by the Bcl-2 family. J Cell Sci 122(Pt4):437–441CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    De Mejia EG, Prisecaru VI (2005) Lectins as bioactive proteins: a potential in cancer treatment. Crit Rev Food Sci Nutr 45(6):425–445CrossRefPubMedGoogle Scholar
  14. 14.
    Francis F, Jaber K, Colinet F, Portetelle D, Haubruge E (2011) Purification of a new fungal mannose-specific lectin from Penicillium chrysogenum and its aphicidal properties. Fungal Biol 115(11):1093–1099CrossRefPubMedGoogle Scholar
  15. 15.
    Shao B, Wang S, Zhou J, Ke L, Rao P (2011) A novel lectin from fresh rhizome of Alismaorientale (Sam.) Juzep. Process Biochem (Oxford, UK) 46:1554–1559CrossRefGoogle Scholar
  16. 16.
    Hakomori S (2002) Glycosylation defining cancer malignancy: new wine in an old bottle. Proc Natl Acad Sci USA 99(16):10231–10233CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Estaquier J, Vallette F, Vayssiere JL, Mignotte B (2012) The mitochondrial pathways of apoptosis. Adv Exp Med Biol 942:157–183CrossRefPubMedGoogle Scholar
  18. 18.
    Salvesan GS, Dixit VM (1999) Caspase activation: the induced-proximity model. Proc Natl Acad Sci USA 96(20):10964–10967CrossRefGoogle Scholar
  19. 19.
    Chan YS, Wong JH, Fang EF, Pan W, Ng TB (2012) Isolation of a glucosamine binding leguminous lectin with mitogenic activity towards splenocytes and anti-proliferative activity towards tumor cells. PLoS One 7(6):1–13Google Scholar
  20. 20.
    Lam SK, Ng TB (2010) First report of a haemagglutinin-induced apoptotic pathway in breast cancer cells. Biosci Rep 30(5):307–317CrossRefPubMedGoogle Scholar
  21. 21.
    Luo Y, Liu X, Lin F, Liao L, Deng Y, Zeng L, Zeng Q (2018) Cloning of a novel lectin from Artocarpus lingnanensis that induces apoptosis in human B-lymphoma cells. Biosci Biotechnol Biochem 82(2):258–267CrossRefPubMedGoogle Scholar
  22. 22.
    Luo X, Budihardjo I, Zou H, Slaughter C, Wang X (1998) Bid, a Bcl2 interacting protein, mediates cytochrome c release from mitochondria in response to activation of cell surface death receptors. Cell 94(4):481–490CrossRefPubMedGoogle Scholar
  23. 23.
    Zhang CZ, Fang EF, Zhang HT, Liu LL, Yun JP (2015) Momordica charantia lectin exhibits antitumor activity towards hepatocellular carcinoma. Investig New Drugs 33(1):1–11CrossRefGoogle Scholar
  24. 24.
    Munoz-Pinedo C, Guio-Carrion A, Goldstein JC, Fitzgerald P, Newmeyer DD, Green DR (2006) Different mitochondrial intermembrane space proteins are released during apoptosis in a manner that is coordinately initiated but can vary induration. Proc Natl Acad Sci USA 103(31):11573–11578CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    Ouyang L, Chen Y, Wang XY, Lu RF, Zhang SY, Tian M, Xie T, Liu B, He G (2014) Polygonatum odoratum lectin induces apoptosis and autophagy via targeting EGFR-mediated Ras-Raf-MEK-ERK pathway in human MCF-7 breast cancer cells. Phytomedicine 21(12):1658–1665CrossRefPubMedGoogle Scholar
  26. 26.
    Lei HY, Chang CP (2009) Lectin of Concanavalin A as an anti-hepatoma therapeutic agent. J Biomed Sci 16:10CrossRefPubMedPubMedCentralGoogle Scholar
  27. 27.
    Liu B, Wu JM, Li J, Liu JJ, Li WW, Li CY, Xu HL, Bao JK (2010) Polygonatum cyrtonema lectin induces murine fibrosarcoma L929 cell apoptosis via blocking Ras–Raf and PI3K–Akt signaling pathways. Biochimie 92(12):1934–1938CrossRefPubMedGoogle Scholar
  28. 28.
    Liu B, Cheng Y, Zhang B, Bian HJ, Bao JK (2009) Polygonatum cyrtonema lectin induces apoptosis and autophagy in human melanoma A375 cells through a mitochondria-mediated ROS–p38–p53 pathway. Cancer Lett 275(1):54–60CrossRefPubMedGoogle Scholar
  29. 29.
    Dasmahapatra G, Lembersky D, Kramer L, Fisher RI, Friedberg J, Dent P, Grant S (2010) The pan-HDAC inhibitor vorinostat potentiates the activity of the proteasome inhibitor carfilzomib in human DLBCL cells in vitro and in vivo. Blood 115(22):4478–4487CrossRefPubMedPubMedCentralGoogle Scholar
  30. 30.
    Wilhelm SM, Carter C, Tang L, Wilkie D, McNabola A, Rong H et al (2004) BAY 43-9006 exhibits broad spectrum oral antitumor activity and targets the RAF/MEK/ERK pathway and receptor tyrosine kinases involved in tumor progression and angiogenesis. Cancer Res 64(19):7099–7109CrossRefPubMedGoogle Scholar
  31. 31.
    Castro J, Ribo M, Navarro S, Nogues MV, Vilanova M, Benito A (2011) A human ribonuclease induces apoptosis associated with p21W AF1/CIP1 induction and JNK inactivation. BMC Cancer 11:9CrossRefPubMedPubMedCentralGoogle Scholar
  32. 32.
    Park J, Kim I, Oh YJ, Lee K, Han PL, Choi EJ (1997) Activation of c-Jun N-terminal kinase antagonizes an anti-apoptotic action of Bcl-2. J Biol Chem 272(27):16725–16728CrossRefPubMedGoogle Scholar
  33. 33.
    Markou T, Dowling AA, Kelly T, Lazou A (2009) Regulation of Bcl-2 phosphorylation in response to oxidative stress in cardiac myocytes. Free Radic Res 43(9):809–816CrossRefPubMedGoogle Scholar

Copyright information

© The Japanese Society of Pharmacognosy and Springer Japan KK, part of Springer Nature 2018

Authors and Affiliations

  • Linjie Zeng
    • 2
  • Lu Li
    • 1
  • Qiyan Zeng
    • 1
  • Yong Deng
    • 1
  • Lijun Yin
    • 1
  • Liejun Liao
    • 1
  1. 1.Department of Biochemistry and Molecular BiologyGuangxi Medical UniversityNanningPeople’s Republic of China
  2. 2.Department of Orthopaedics, Chinese and WesternOrthopaedics Hospital of GuigangGuigangPeople’s Republic of China

Personalised recommendations