Login Register Cart 0
Generic placeholder image

Anti-Cancer Agents in Medicinal Chemistry

Editor-in-Chief

ISSN (Print): 1871-5206
ISSN (Online): 1875-5992

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Research Article

In Vitro Inhibitory Effect of Recombinant Human Calprotectin on Nalm6 Leukemia Cell Line

Author(s): Samira Charkhizadeh, Mehdi Imani, Nematollah Gheibi, Fateme Shabaani, Akbar Nikpajouh and Mohammad R. Rezvany*

Volume 20, Issue 8, 2020

Page: [951 - 962] Pages: 12

DOI: 10.2174/1871520620666200331101209

Price: $65

Abstract

Background & Purpose: In evaluating new drugs for the treatment of various types of cancer, investigations have been made to discover a variety of anti-tumor compounds with less side effects on normal cells. Investigations have shown that the heterodimers S100A8 and S100A9 inhibit the enzyme casein kinase 2 and then prevent the activation of the E7 oncoprotein. Therefore, the aim of this study was to evaluate the effect of calprotectin as an antitumor compound on the Nalm6 (B cell precursor leukemia cell line).

Materials & Methods: Transformation of genes encoding S100A8 and S100A9 human, designed in the pQE32 plasmid, was performed by the thermal shock method into E. coli M15 bacteria. After bacterial growth in LB medium, the expression of two S100A8 and S100A9 subunits, the solubility of the protein by SDS-PAGE method was determined. Finally, the S100A8 / A9 complex was equally placed in the microtube. In the next step, the cytotoxic effects of calprotectin produced on the Nalm6 cell line were evaluated using the wst1 test. Then, the apoptosis in these cells was measured using flow cytometry methods with Annexin-V coloration.

Results: In the current study, the results showed that the cytotoxic effects of Calprotectin are time and concentration- dependent. Therefore, it can reduce the tumor expression and had a beneficial effect by induced apoptosis in Nalm6 cell line.

Conclusion: Calprotectin has an anti-tumor effect on the Nalm6 cell line by increasing apoptosis.

Keywords: Calprotectin, S100A8, S100A9, Nalm6, acute lymphoblastic leukemia, pQE32 plasmid.

« Previous Next »
Graphical Abstract

[1]
Jemal, A.; Murray, T.; Ward, E.; Samuels, A.; Tiwari, R.C.; Ghafoor, A.; Feuer, E.J.; Thun, M.J. Cancer statistics, 2005. CA Cancer J. Clin., 2005, 55(1), 10-30.
[http://dx.doi.org/10.3322/canjclin.55.1.10] [PMID: 15661684]
[2]
Nakao, M.; Yokota, S.; Iwai, T.; Kaneko, H.; Horiike, S.; Kashima, K.; Sonoda, Y.; Fujimoto, T.; Misawa, S. Internal tandem duplication of the flt3 gene found in acute myeloid leukemia. Leukemia, 1996, 10(12), 1911-1918.
[PMID: 8946930]
[3]
Radich, J.P.; Kopecky, K.J.; Willman, C.L.; Weick, J.; Head, D.; Appelbaum, F.; Collins, S.J. N-ras mutations in adult de novo acute myelogenous leukemia: prevalence and clinical significance. Blood, 1990, 76(4), 801-807.
[http://dx.doi.org/10.1182/blood.V76.4.801.801] [PMID: 2200539]
[4]
Miyoshi, T.; Yamashita, K.; Ohno, T.; Izumi, T.; Takaori-Kondo, A.; Sasada, M.; Uchiyama, T. Familial Mediterranean fever gene as a possible modifier of Sweet syndrome with chronic myelogenous leukemia. Acta Haematol., 2008, 120(1), 57-62.
[http://dx.doi.org/10.1159/000158578] [PMID: 18824843]
[5]
Mitchell, L.G.; Andrew, M.; Hanna, K.; Abshire, T.; Halton, J.; Anderson, R.; Cherrick, I.; Desai, S.; Mahoney, D.; McCuster, P.; Wu, J.; Dahl, G.; Chait, P.; de Veber, G.; Lee, K.J.; Mikulis, D.; Ginsberg, J.; Way, C. A prospective cohort study determining the prevalence of thrombotic events in children with acute lymphoblastic leukemia and a central venous line who are treated with L-asparaginase: results of the Prophylactic Antithrombin Replacement in Kids with Acute Lymphoblastic Leukemia Treated with Asparaginase (PARKAA) Study. Cancer, 2003, 97(2), 508-516.
[http://dx.doi.org/10.1002/cncr.11042] [PMID: 12518376]
[6]
Uchiyama, T.; Yodoi, J.; Sagawa, K.; Takatsuki, K.; Uchino, H. Adult T-cell leukemia: clinical and hematologic features of 16 cases. Blood, 1977, 50(3), 481-492.
[http://dx.doi.org/10.1182/blood.V50.3.481.481] [PMID: 301762]
[7]
Hanahan, D.; Bergers, G.; Bergsland, E. Less is more, regularly: metronomic dosing of cytotoxic drugs can target tumor angiogenesis in mice. J. Clin. Invest., 2000, 105(8), 1045-1047.
[http://dx.doi.org/10.1172/JCI9872] [PMID: 10772648]
[8]
Røseth, A.G.; Fagerhol, M.K.; Aadland, E.; Schjønsby, H. Assessment of the neutrophil dominating protein calprotectin in feces. A methodologic study. Scand. J. Gastroenterol., 1992, 27(9), 793-798.
[http://dx.doi.org/10.3109/00365529209011186] [PMID: 1411288]
[9]
Urban, C.F.; Ermert, D.; Schmid, M.; Abu-Abed, U.; Goosmann, C.; Nacken, W.; Brinkmann, V.; Jungblut, P.R.; Zychlinsky, A. Neutrophil extracellular traps contain calprotectin, a cytosolic protein complex involved in host defense against Candida albicans. PLoS Pathog., 2009, 5(10)e1000639
[http://dx.doi.org/10.1371/journal.ppat.1000639] [PMID: 19876394]
[10]
Yui, S.; Nakatani, Y.; Mikami, M. Calprotectin (S100A8/S100A9), an inflammatory protein complex from neutrophils with a broad apoptosis-inducing activity. Biol. Pharm. Bull., 2003, 26(6), 753-760.
[http://dx.doi.org/10.1248/bpb.26.753] [PMID: 12808281]
[11]
Liu, J.Z.; Jellbauer, S.; Poe, A.J.; Ton, V.; Pesciaroli, M.; Kehl-Fie, T.E.; Restrepo, N.A.; Hosking, M.P.; Edwards, R.A.; Battistoni, A.; Pasquali, P.; Lane, T.E.; Chazin, W.J.; Vogl, T.; Roth, J.; Skaar, E.P.; Raffatellu, M. Zinc sequestration by the neutrophil protein calprotectin enhances Salmonella growth in the inflamed gut. Cell Host Microbe, 2012, 11(3), 227-239.
[http://dx.doi.org/10.1016/j.chom.2012.01.017] [PMID: 22423963]
[12]
Mørk, G.; Schjerven, H.; Mangschau, L.; Søyland, E.; Brandtzaeg, P. Proinflammatory cytokines upregulate expression of calprotectin (L1 protein, MRP-8/MRP-14) in cultured human keratinocytes. Br. J. Dermatol., 2003, 149(3), 484-491.
[http://dx.doi.org/10.1046/j.1365-2133.2003.05536.x] [PMID: 14510979]
[13]
Leach, S.T.; Yang, Z.; Messina, I.; Song, C.; Geczy, C.L.; Cunningham, A.M.; Day, A.S. Serum and mucosal S100 proteins, calprotectin (S100A8/S100A9) and S100A12, are elevated at diagnosis in children with inflammatory bowel disease. Scand. J. Gastroenterol., 2007, 42(11), 1321-1331.
[http://dx.doi.org/10.1080/00365520701416709] [PMID: 17852869]
[14]
Gray, R.D.; Imrie, M.; Boyd, A.C.; Porteous, D.; Innes, J.A.; Greening, A.P. Sputum and serum calprotectin are useful biomarkers during CF exacerbation. J. Cyst. Fibros., 2010, 9(3), 193-198.
[http://dx.doi.org/10.1016/j.jcf.2010.01.005] [PMID: 20299288]
[15]
Brandtzaeg, P.; Dale, I.; Gabrielsen, T.Ø. The leucocyte protein L1 (calprotectin): usefulness as an immunohistochemical marker antigen and putative biological function. Histopathology, 1992, 21(2), 191-196.
[http://dx.doi.org/10.1111/j.1365-2559.1992.tb00374.x] [PMID: 1505941]
[16]
Desjardins, P.; Hansen, J.B.; Allen, M. Microvolume protein concentration determination using the NanoDrop 2000c spectrophotometer. J. Vis. Exp., 2009, 33, 1-3.
[17]
Hingorani, R.; Deng, J.; Elia, J.; Mclntyre, C.; Mittar, D. Detection of apoptosis using the BD Annexin V FITC assay on the BD FACSVerse system. BD Biosciences, 2011, 23(130), 21-28.
[18]
Go, V.; Wong, D.; Butrum, W.; Wong, D.; Butrum, R. Diet, nutrient and cancer preventation. Nutrition, 2001, 139, 3121-3126.
[http://dx.doi.org/10.1093/jn/131.11.3121S]
[19]
Zali, H.; Marashi, S-A.; Rezaei-Tavirani, M.; Toossi, P.; Rahmati-Roodsari, M.; Shokrgozar, M.A. On the mechanism of apoptosis-inducing activity of human calprotectin: zinc sequestration, induction of a signaling pathway, or something else? Med. Hypotheses, 2007, 68(5), 1012-1015.
[http://dx.doi.org/10.1016/j.mehy.2006.09.056] [PMID: 17126494]
[20]
Tavirani, M.R.; Zali, H.; Nasiri, S.; Shokrgozar, M. Human calprotectin, a potent anticancer with minimal side effect. Iran. J. Cancer Prev., 2009, 2(4)
[21]
Yui, S.; Yang, D.; Mikami, M.; Yamazaki, M. Characterization of cell growth-inhibitory factor in inflammatory peritoneal exudate cells of rats. Microbiol. Immunol., 1993, 37(12), 961-969.
[http://dx.doi.org/10.1111/j.1348-0421.1993.tb01730.x] [PMID: 8133801]
[22]
Yui, S.; Mikami, M.; Yamazaki, M. Purification and characterization of the cytotoxic factor in rat peritoneal exudate cells: its identification as the calcium binding protein complex, calprotectin. J. Leukoc. Biol., 1995, 58(3), 307-316.
[http://dx.doi.org/10.1002/jlb.58.3.307] [PMID: 7665986]
[23]
Yui, S.; Nakatani, Y.; Hunter, M.J.; Chazin, W.J.; Yamazaki, M. Implication of extracellular zinc exclusion by recombinant human calprotectin (MRP8 and MRP14) from target cells in its apoptosis-inducing activity. Mediators Inflamm., 2002, 11(3), 165-172.
[http://dx.doi.org/10.1080/09622935020138208] [PMID: 12137245]
[24]
Yarandi, N.; Zali, H.; Shokrgozar, M.A.; Mansouri, V.; Shahani, M.; Rostami, A.; Heidari, S. Study of apoptosis inducing activity of calprotectin on fibroblast cell. J. Paramed. Sci., 2010, 1(1), 9-15.
[25]
Ghavami, S.; Kerkhoff, C.; Los, M.; Hashemi, M.; Sorg, C.; Karami-Tehrani, F. Mechanism of apoptosis induced by S100A8/A9 in colon cancer cell lines: the role of ROS and the effect of metal ions. J. Leukoc. Biol., 2004, 76(1), 169-175.
[http://dx.doi.org/10.1189/jlb.0903435] [PMID: 15075348]
[26]
Chang, M.H.; Chou, J.W.; Chen, S.M.; Tsai, M.C.; Sun, Y.S.; Lin, C.C.; Lin, C.P. Faecal calprotectin as a novel biomarker for differentiating between inflammatory bowel disease and irritable bowel syndrome. Mol. Med. Rep., 2014, 10(1), 522-526.
[http://dx.doi.org/10.3892/mmr.2014.2180] [PMID: 24788223]
[27]
Elnawsra, O.; Fok, I.; Sparrow, M.; Gibson, P.; Andrews, J.; Connor, S. Faecal calprotectin: current usage and perceived beneficial effects of third-party funding on rates of colonoscopy by Australian gastroenterologists. Intern. Med. J., 2016, 46(5), 590-595.
[http://dx.doi.org/10.1111/imj.13056] [PMID: 26946938]
[28]
Rangel-Sosa, M.M.; Aguilar-Córdova, E.; Rojas-Martínez, A. Immunotherapy and gene therapy as novel treatments for cancer. Colomb. Med., 2017, 48(3), 138-147.
[PMID: 29213157]

Rights & Permissions Print Cite
Article Metrics
15
© 2024 Bentham Science Publishers | Privacy Policy