Login Register Cart 0
Generic placeholder image

Protein & Peptide Letters

Editor-in-Chief

ISSN (Print): 0929-8665
ISSN (Online): 1875-5305

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

A Short Cationic Peptide Derived from Cecropin and Melittin Peptides Induce Apoptosis in Jurkat and Raji Leukemia Cell Lines

Author(s): Mustafa Ebrahimdoust, Hamideh Malek Hayati, Mehrdad Moosazadeh Moghaddam* and Mehran Bahreini

Volume 30, Issue 6, 2023

Published on: 30 May, 2023

Page: [477 - 485] Pages: 9

DOI: 10.2174/0929866530666230512142826

Price: $65

Abstract

Background: The creation of brand-new, potent, and less harmful medications to treat leukemia is urgently needed. Antimicrobial peptides (AMPs) have drawn a lot of interest as potential substitutes for chemotherapy.

Objective: In the present investigation, the anticancer activity of CM11, a short cationic AMP, was assessed on Jurkat and Raji leukemia cell lines and peripheral blood mononuclear cells (PBMCs).

Methods: Different CM11 doses were applied to the Jurkat and Raji cell lines and PBMCs throughout a 24-hour period. The impact of the CM11 on cell viability and toxicity was assessed using an MTT assay. Flow cytometry and Real-Time PCR were used to analyze the effect of this peptide on apoptotic/necrosis pathways and assess the ratio expression of the P53 and Bcl-2 genes, respectively.

Results: Despite the fact that peptide toxicity was successful in a variety of cell lines, cancer cells were more sensitive to the medication. The survival of Jurkat and Raji cell lines treated with 32 μg/ml peptide was 47% and 51%, respectively, while the survival of normal PBMC cells was about 65%. According to flow cytometry, Jurkat and Raji cells exposed to peptide had much greater levels of apoptosis than PBMCs. Peptide-treated cells were associated with increased expression of P53 the gene and decreased expression of the Bcl-2 gene.

Conclusion: These results revealed that the CM11 caused more cytotoxicity to leukemia Raji and Jurkat leukemia cells compared to the normal cells by apoptosis pathway. Our findings demonstrated the potential of CM11 peptide to develop as a new antileukemic agent.

Keywords: Leukemia, antimicrobial peptide, anticancer, apoptosis, CM11 peptide, P53 gene.

« Previous Next »
Graphical Abstract

[1]
Sung, H.; Ferlay, J.; Siegel, R.L.; Laversanne, M.; Soerjomataram, I.; Jemal, A.; Bray, F. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J. Clin., 2021, 71(3), 209-249.
[http://dx.doi.org/10.3322/caac.21660] [PMID: 33538338]
[2]
Szebeni, G.; Balog, J.; Demjén, A.; Alföldi, R.; Végi, V.; Fehér, L.; Mán, I.; Kotogány, E.; Gubán, B.; Batár, P.; Hackler, L., Jr; Kanizsai, I.; Puskás, L. Imidazo [1,2-b] pyrazole-7-carboxamides induce apoptosis in human leukemia cells at nanomolar concentrations. Molecules, 2018, 23(11), 2845.
[http://dx.doi.org/10.3390/molecules23112845] [PMID: 30388846]
[3]
Aldoss, I.; Stein, A.S. Advances in adult acute lymphoblastic leukemia therapy. Leuk. Lymphoma, 2018, 59(5), 1033-1050.
[http://dx.doi.org/10.1080/10428194.2017.1354372] [PMID: 28745565]
[4]
Papo, N.; Shai, Y. Host defense peptides as new weapons in cancer treatment. Cell. Mol. Life Sci., 2005, 62(7-8), 784-790.
[http://dx.doi.org/10.1007/s00018-005-4560-2] [PMID: 15868403]
[5]
Emadi, A.; Gore, S.D. Arsenic trioxide — An old drug rediscovered. Blood Rev., 2010, 24(4-5), 191-199.
[http://dx.doi.org/10.1016/j.blre.2010.04.001] [PMID: 20471733]
[6]
Ponnusamy, L.; Mahalingaiah, P.K.S.; Singh, K.P. Chronic oxidative stress increases resistance to doxorubicin-induced cytotoxicity in renal carcinoma cells potentially through epigenetic mechanism. Mol. Pharmacol., 2016, 89(1), 27-41.
[http://dx.doi.org/10.1124/mol.115.100206] [PMID: 26519223]
[7]
Zhou, S.; Palmeira, C.M.; Wallace, K.B. Doxorubicin-induced persistent oxidative stress to cardiac myocytes. Toxicol. Lett., 2001, 121(3), 151-157.
[http://dx.doi.org/10.1016/S0378-4274(01)00329-0] [PMID: 11369469]
[8]
Keeney, J.T.R.; Ren, X.; Warrier, G.; Noel, T.; Powell, D.K.; Brelsfoard, J.M.; Sultana, R.; Saatman, K.E.; Clair, D.K.S.; Butterfield, D.A. Doxorubicin-induced elevated oxidative stress and neurochemical alterations in brain and cognitive decline: protection by MESNA and insights into mechanisms of chemotherapy-induced cognitive impairment (“chemobrain”). Oncotarget, 2018, 9(54), 30324-30339.
[http://dx.doi.org/10.18632/oncotarget.25718] [PMID: 30100992]
[9]
Gaspar, D.; Veiga, A.S.; Castanho, M.A.R.B. From antimicrobial to anticancer peptides. A review. Front. Microbiol., 2013, 4, 294.
[http://dx.doi.org/10.3389/fmicb.2013.00294] [PMID: 24101917]
[10]
Moghaddam, M.M.; Aghamollaei, H.; Kooshki, H.; Barjini, K.A.; Mirnejad, R.; Choopani, A. The development of antimicrobial peptides as an approach to prevention of antibiotic resistance. Rev. Med. Microbiol., 2015, 26(3), 98-110.
[http://dx.doi.org/10.1097/MRM.0000000000000032]
[11]
Deslouches, B.; Di, Y.P. Antimicrobial peptides with selective antitumor mechanisms: Prospect for anticancer applications. Oncotarget, 2017, 8(28), 46635-46651.
[http://dx.doi.org/10.18632/oncotarget.16743] [PMID: 28422728]
[12]
Qin, Y.; Qin, Z.D.; Chen, J.; Cai, C.G.; Li, L.; Feng, L.Y.; Wang, Z.; Duns, G.J.; He, N.Y.; Chen, Z.S.; Luo, X.F. From antimicrobial to anticancer peptides: The transformation of peptides. Recent Patents Anticancer Drug Discov., 2019, 14(1), 70-84.
[http://dx.doi.org/10.2174/1574892814666190119165157] [PMID: 30663573]
[13]
Aaghaz, S.; Gohel, V.; Kamal, A. Peptides as potential anticancer agents. Curr. Top. Med. Chem., 2019, 19(17), 1491-1511.
[http://dx.doi.org/10.2174/1568026619666190125161517] [PMID: 30686254]
[14]
Kumar, P.; Kizhakkedathu, J.; Straus, S. Antimicrobial peptides: Diversity, mechanism of action and strategies to improve the activity and biocompatibility in vivo. Biomolecules, 2018, 8(1), 4.
[http://dx.doi.org/10.3390/biom8010004] [PMID: 29351202]
[15]
Mahlapuu, M.; Håkansson, J.; Ringstad, L.; Björn, C. Antimicrobial peptides: An emerging category of therapeutic agents. Front. Cell. Infect. Microbiol., 2016, 6, 194.
[http://dx.doi.org/10.3389/fcimb.2016.00194] [PMID: 28083516]
[16]
Soblosky, L.; Ramamoorthy, A.; Chen, Z. Membrane interaction of antimicrobial peptides using E. coli lipid extract as model bacterial cell membranes and SFG spectroscopy. Chem. Phys. Lipids, 2015, 187, 20-33.
[http://dx.doi.org/10.1016/j.chemphyslip.2015.02.003] [PMID: 25707312]
[17]
Mirnejad, R.; Fasihi-Ramandi, M.; Behmard, E.; Najafi, A.; Moosazadeh, M.M. Interaction of antibacterial CM11 peptide with the gram-positive and gram-negative bacterial membrane models: A molecular dynamics simulations study. Chem. Pap., 2023.
[http://dx.doi.org/10.1007/s11696-023-02735-1]
[18]
Schweizer, F. Cationic amphiphilic peptides with cancer-selective toxicity. Eur. J. Pharmacol., 2009, 625(1-3), 190-194.
[http://dx.doi.org/10.1016/j.ejphar.2009.08.043] [PMID: 19835863]
[19]
Moravej, H.; Moravej, Z.; Yazdanparast, M.; Heiat, M.; Mirhosseini, A.; Moosazadeh, M.M.; Mirnejad, R. Antimicrobial peptides: Features, action, and their resistance mechanisms in bacteria. Microb. Drug Resist., 2018, 24(6), 747-767.
[http://dx.doi.org/10.1089/mdr.2017.0392] [PMID: 29957118]
[20]
Moghaddam, M.M.; Abolhassani, F.; Babavalian, H.; Mirnejad, R.; Azizi Barjini, K.; Amani, J. Comparison of in vitro antibacterial activities of two cationic peptides CM15 and CM11 against five pathogenic bacteria: Pseudomonas aeruginosa, Staphylococcus aureus, Vibrio cholerae, Acinetobacter baumannii, and Escherichia coli. Probiotics Antimicrob. Proteins, 2012, 4(2), 133-139.
[http://dx.doi.org/10.1007/s12602-012-9098-7] [PMID: 26781855]
[21]
Andreu, D.; Ubach, J.; Boman, A.; Wåhlin, B.; Wade, D.; Merrifield, R.B.; Boman, H.G. Shortened cecropin A-melittin hybrids significant size reduction retains potent antibiotic activity. FEBS Lett., 1992, 296(2), 190-194.
[http://dx.doi.org/10.1016/0014-5793(92)80377-S] [PMID: 1733777]
[22]
Juvvadi, P.; Vunnam, S.; Merrifield, E.L.; Boman, H.G.; Merrifield, R.B. Hydrophobic effects on antibacterial and channel-forming properties of cecropin A-melittin hybrids. J. Pept. Sci., 1996, 2(4), 223-232.
[23]
Mancheño, J.M.; Oñaderra, M.; Martínez del Pozo, A.; Díaz-Achirica, P.; Andreu, D.; Rivas, L.; Gavilanes, J.G. Release of lipid vesicle contents by an antibacterial cecropin A-melittin hybrid peptide. Biochemistry, 1996, 35(30), 9892-9899.
[http://dx.doi.org/10.1021/bi953058c] [PMID: 8703963]
[24]
Moghaddam, M.M.; Barjini, K.A.; Ramandi, M.F.; Amani, J. Investigation of the antibacterial activity of a short cationic peptide against multidrug-resistant Klebsiella pneumoniae and Salmonella typhimurium strains and its cytotoxicity on eukaryotic cells. World J. Microbiol. Biotechnol., 2014, 30(5), 1533-1540.
[http://dx.doi.org/10.1007/s11274-013-1575-y] [PMID: 24323118]
[25]
Felício, M.R.; Silva, O.N.; Gonçalves, S.; Santos, N.C.; Franco, O.L. Peptides with dual antimicrobial and anticancer activities. Front Chem., 2017, 5, 5.
[http://dx.doi.org/10.3389/fchem.2017.00005] [PMID: 28271058]
[26]
Mohammadi Azad, Z.; Moravej, H.; Fasihi-Ramandi, M.; Masjedian, F.; Nazari, R.; Mirnejad, R.; Moosazadeh, M.M. in vitro synergistic effects of a short cationic peptide and clinically used antibiotics against drug-resistant isolates of Brucella melitensis. J. Med. Microbiol., 2017, 66(7), 919-926.
[http://dx.doi.org/10.1099/jmm.0.000524] [PMID: 28699872]
[27]
Fuss, I.J.; Kanof, M.E.; Smith, P.D.; Zola, H. Isolation of whole mononuclear cells from peripheral blood and cord blood. Curr. Protoc. Immunol., 2009, 85(1), 7-8.
[http://dx.doi.org/10.1002/0471142735.im0701s85]
[28]
Moravej, H.; Fasihi-Ramandi, M.; Moghaddam, M.M.; Mirnejad, R. Cytotoxicity and antibacterial effect of Trp-substituted CM11 cationic peptide against drug-resistant isolates of Brucella melitensis alone and in combination with recommended antibiotics. Int. J. Pept. Res. Ther., 2019, 25(1), 235-245.
[http://dx.doi.org/10.1007/s10989-017-9658-5]
[29]
Saaed, H.K.; Mahmood, M.A.; Khoshnaw, N. Quantitative real time PCR analysis of apoptotic gene expression in chronic lymphocytic leukemia patients and their relationships with chemosensitivity. Applied Cancer Research, 2017, 37(1), 8.
[http://dx.doi.org/10.1186/s41241-017-0014-z]
[30]
Hoskin, D.W.; Ramamoorthy, A. Studies on anticancer activities of antimicrobial peptides. Biochim. Biophys. Acta Biomembr., 2008, 1778(2), 357-375.
[http://dx.doi.org/10.1016/j.bbamem.2007.11.008]
[31]
Ebrahimdoost, M.; Mohammadi, M.; Obeidi, N.; Mohammadi, S.A.; Khamisipour, G. Pleurocidin-like peptide from poecilia mexicana fish induces selective cytotoxicity in leukemia jurkat cells through the apoptosis pathway. Cell J., 2023, 25(2), 76-84.
[32]
McMillan, K.A.M.; Coombs, M.R.P. Investigating potential applications of the fish anti-microbial peptide pleurocidin: A systematic review. Pharmaceuticals, 2021, 14(7), 687.
[http://dx.doi.org/10.3390/ph14070687] [PMID: 34358113]
[33]
Zhang, H.; Han, D.; Lv, T.; Liu, K.; Yang, Y.; Xu, X.; Chen, Y. Novel peptide myristoly-CM4 induces selective cytotoxicity in leukemia K562/MDR and Jurkat cells by necrosis and/or apoptosis pathway. Drug Des. Devel. Ther., 2019, 13, 2153-2167.
[http://dx.doi.org/10.2147/DDDT.S207224] [PMID: 31308628]
[34]
Chen, Y.Q.; Min, C.; Sang, M.; Han, Y.Y.; Ma, X.; Xue, X.Q.; Zhang, S.Q. A cationic amphiphilic peptide ABP-CM4 exhibits selective cytotoxicity against leukemia cells. Peptides, 2010, 31(8), 1504-1510.
[http://dx.doi.org/10.1016/j.peptides.2010.05.010] [PMID: 20493915]
[35]
Chen, Y.; Guarnieri, M.T.; Vasil, A.I.; Vasil, M.L.; Mant, C.T.; Hodges, R.S. Role of peptide hydrophobicity in the mechanism of action of alpha-helical antimicrobial peptides. Antimicrob. Agents Chemother., 2007, 51(4), 1398-1406.
[http://dx.doi.org/10.1128/AAC.00925-06] [PMID: 17158938]
[36]
Ebrahimdoost, M.; Mohammadi, M.; Obeidi, N.; Mohammadi, S.A. A pleurocidin-like peptide from Poecilia Mexicana fish induces selective cytotoxicity in leukemia Jurkat cells through apoptosis pathway. Cell Journal (Yakhteh). Cell J., 2022, 25(2), 76-84.
[37]
Yan, J.; Liang, X.; Bai, C.; Zhou, L.; Li, J.; Wang, K.; Tang, Y.; Zhao, L. NK-18, a promising antimicrobial peptide: Anti-multidrug resistant leukemia cells and LPS neutralizing properties. Biochimie, 2018, 147, 143-152.
[http://dx.doi.org/10.1016/j.biochi.2018.02.001] [PMID: 29427740]
[38]
Sang, M.; Zhang, J.; Zhuge, Q. Selective cytotoxicity of the antibacterial peptide ABP- dHC -Cecropin A and its analog towards leukemia cells. Eur. J. Pharmacol., 2017, 803, 138-147.
[http://dx.doi.org/10.1016/j.ejphar.2017.03.054] [PMID: 28347740]
[39]
Hilchie, A.L.; Conrad, D.M.; Power Coombs, M.R.; Zemlak, T.; Doucette, C.D.; Liwski, R.S.; Hoskin, D.W. Pleurocidin-family cationic antimicrobial peptides mediate lysis of multiple myeloma cells and impair the growth of multiple myeloma xenografts. Leuk. Lymphoma, 2013, 54(10), 2255-2262.
[http://dx.doi.org/10.3109/10428194.2013.770847] [PMID: 23350892]
[40]
Morash, M.G.; Douglas, S.E.; Robotham, A.; Ridley, C.M.; Gallant, J.W.; Soanes, K.H. The zebrafish embryo as a tool for screening and characterizing pleurocidin host-defense peptides as anti-cancer agents. Dis. Model. Mech., 2011, 4(5), 622-633.
[http://dx.doi.org/10.1242/dmm.007310] [PMID: 21729875]
[41]
Szlasa, W.; Zendran, I.; Zalesińska, A.; Tarek, M.; Kulbacka, J. Lipid composition of the cancer cell membrane. J. Bioenerg. Biomembr., 2020, 52(5), 321-342.
[http://dx.doi.org/10.1007/s10863-020-09846-4] [PMID: 32715369]
[42]
Salmoiraghi, S.; Rambaldi, A.; Spinelli, O. TP53 in adult acute lymphoblastic leukemia. Leuk. Lymphoma, 2018, 59(4), 778-789.
[http://dx.doi.org/10.1080/10428194.2017.1344839] [PMID: 28679301]
[43]
Kroemer, G. The proto-oncogene Bcl-2 and its role in regulating apoptosis. Nat. Med., 1997, 3(6), 614-620.
[http://dx.doi.org/10.1038/nm0697-614] [PMID: 9176486]
[44]
Huang, Y.; Feng, Q.; Yan, Q.; Hao, X.; Chen, Y. Alpha-helical cationic anticancer peptides: A promising candidate for novel anticancer drugs. Mini Rev. Med. Chem., 2015, 15(1), 73-81.
[http://dx.doi.org/10.2174/1389557514666141107120954] [PMID: 25382016]
[45]
Ren, S.X.; Cheng, A.S.L.; To, K.F.; Tong, J.H.M.; Li, M.S.; Shen, J.; Wong, C.C.M.; Zhang, L.; Chan, R.L.Y.; Wang, X.J.; Ng, S.S.M.; Chiu, L.C.M.; Marquez, V.E.; Gallo, R.L.; Chan, F.K.L.; Yu, J.; Sung, J.J.Y.; Wu, W.K.K.; Cho, C.H. Host immune defense peptide LL-37 activates caspase-independent apoptosis and suppresses colon cancer. Cancer Res., 2012, 72(24), 6512-6523.
[http://dx.doi.org/10.1158/0008-5472.CAN-12-2359] [PMID: 23100468]
[46]
Han, Y.; Lu, M.; Zhou, J. Buforin IIb induces androgen-independent prostate cancer cells apoptosis though p53 pathway in vitro. Toxicon, 2019, 168, 16-21.
[http://dx.doi.org/10.1016/j.toxicon.2019.06.016] [PMID: 31229626]
[47]
Wang, C.; Zhou, Y.; Li, S.; Li, H.; Tian, L.; Wang, H.; Shang, D. Anticancer mechanisms of temporin-1CEa, an amphipathic α-helical antimicrobial peptide, in Bcap-37 human breast cancer cells. Life Sci., 2013, 92(20-21), 1004-1014.
[http://dx.doi.org/10.1016/j.lfs.2013.03.016] [PMID: 23583573]
[48]
Jiang, R.; Lönnerdal, B. Bovine lactoferrin and lactoferricin exert antitumor activities on human colorectal cancer cells (HT-29) by activating various signaling pathways. Biochem. Cell Biol., 2017, 95(1), 99-109.
[http://dx.doi.org/10.1139/bcb-2016-0094] [PMID: 28169560]
[49]
Mader, J.S.; Mookherjee, N.; Hancock, R.E.W.; Bleackley, R.C. The human host defense peptide LL-37 induces apoptosis in a calpain- and apoptosis-inducing factor-dependent manner involving Bax activity. Mol. Cancer Res., 2009, 7(5), 689-702.
[http://dx.doi.org/10.1158/1541-7786.MCR-08-0274] [PMID: 19435812]
[50]
Chen, X.; Zou, X.; Qi, G.; Tang, Y.; Guo, Y.; Si, J. Roles and mechanisms of human cathelicidin LL-37 in cancer. Cell. Physiol. Biochem., 2018, 47(3), 1060-1073.
[51]
Taghipour-Sabzevar, V.; Sharifi, T.; Bagheri-Khoulenjani, S.; Goodarzi, V.; Kooshki, H.; Halabian, R.; Moosazadeh, M.M. Targeted delivery of a short antimicrobial peptide against CD44-overexpressing tumor cells using hyaluronic acid-coated chitosan nanoparticles: An in vitro study. J. Nanopart. Res., 2020, 22(5), 99.
[http://dx.doi.org/10.1007/s11051-020-04838-2]

Rights & Permissions Print Cite
Article Metrics
30
3
Wayfinder Image
© 2024 Bentham Science Publishers | Privacy Policy