Mitogenic activity of Artocarpus lingnanensis lectin and its apoptosis induction in Jurkat T cells
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.
KeywordsLectin Glycoprotein Mitogenic activity Apoptosis Leukemia
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.
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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.
- 7.Zhang XS, Wu ZY (1988) Flora reipublicae Popularis Sinicae, vol 23. Beijing Science Press, Beijing, p 53Google Scholar
- 10.Editorial Committee of the Chinese Materia Medica (1999) Chinese materia medica, vol 2. Shanghai Science and Technology Publishing Press, Shanghai, p 467Google Scholar
- 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
- 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
- 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