Share This Article:

The Cytotoxic Effect of Cecropin A and Cecropin B on the MDA-MB-231 and M14K Tumour Cell Lines

Abstract Full-Text HTML Download Download as PDF (Size:1759KB) PP. 504-515
DOI: 10.4236/jbise.2014.78052    2,515 Downloads   3,284 Views   Citations

ABSTRACT

The aim of the present in vitro study was to assess the tumoricidal potential of the following natural peptides belonging to the Cecropin family, namely Cecropin A and B, on a series of tumour cell lines: MDA-MB-231 (breast adenocarcinoma) and M14K (human mesothelioma). The experimental results reveal that the cytotoxic effects of the two peptides depend on their concentration. Their efficiency is significant at 120 μM concentrations and it persists even at 60 μM concentrations. The effects were insignificant at 30 μM concentrations. On the other hand, the cytotoxic potential was not significantly dependant on the type of peptide but more on the type of tumour cell line used. The MDA MB 231 line cells were much more sensitive to the action of Cecropins A and B than the M14K line cells. The prospects brought about by this experimental research consist of the collection of in vitro experimental data on the tumoricidal potential of these natural cytotoxic peptides on tumour cells. This will enable specialists to develop future in vivo experimental models in order to test the antitumor effect of these cytotoxic peptides. The ultimate goal would be the discovery of agents with efficient antitumor properties, i.e. with maximum tumoricidal effects and minimum toxic side effects.

Conflicts of Interest

The authors declare no conflicts of interest.

Cite this paper

Anghel, R. , Jitaru, D. , Badescu, L. , Ciocoiu, M. and Badescu, M. (2014) The Cytotoxic Effect of Cecropin A and Cecropin B on the MDA-MB-231 and M14K Tumour Cell Lines. Journal of Biomedical Science and Engineering, 7, 504-515. doi: 10.4236/jbise.2014.78052.

References

[1] Hoskin, D.W. and Ramamoorthy, A. (2008) Studies on Anticancer Activities of Antimicrobial Peptides. Biochimica et Biophysica Acta (BBA), 1778, 357-375.
http://dx.doi.org/10.1016/j.bbamem.2007.11.008
[2] Reddy, K.V.R., Yedery, R.D. and Aranha, C. (2004) Antimicrobial Peptides: Premises and Promises. International Journal of Antimicrobial Agents, 24, 536-547.
http://dx.doi.org/10.1016/j.ijantimicag.2004.09.005
[3] Dennison, S.R., Whittaker, M., Harris, F. and Phoenix, D.A. (2006) Anticancer Alpha-Helical Peptides and Structure/Function Relationships Underpinning Their Interactions with Tumour Cell Membranes. Current Protein & Peptide Science, 7, 487-499.
http://dx.doi.org/10.2174/138920306779025611
[4] Braff, M.H., Zaiou, M., Fierer, J., Nizet, V. and Gallo, R.L. (2005)Keratinocyte Production of Cathelicidin Provides Direct Activity Against Bacterial Skin Pathogens. Infection and Immunity, 73, 6771-6781.
http://dx.doi.org/10.1128/IAI.73.10.6771-6781.2005
[5] Mor, A. (2000) Peptide-Based Antibiotics: A Potential Answer to Raging Antimicrobial Resistance. Drug Develop- ment Research, 50, 440-447.
http://dx.doi.org/10.1002/1098-2299(200007/08)50:3/4<440::AID-DDR27>3.0.CO;2-4
[6] Hilchie, A., Doucette, C.D., Pinto, D., Patrzykat, A., Douglas, S. and Hoskin, D.W. (2011) Pleurocidin-Family Cationic Antimicrobial Peptides Are Cytolytic for Breast Carcinoma Cells and Prevent Growth of Tumor Xenografts. Breast Cancer Research, 13, R102.
http://dx.doi.org/10.1186/bcr3043
[7] Seth, B.C. and Scandurro, A.B. (2008) Tumors Sound the Alarmin(s). Cancer Research, 68, 6482-6485.
http://dx.doi.org/10.1158/0008-5472.CAN-08-0044
[8] Chamorro, C.I., Weber, G., Grönberg, A., Pivarcsi, A. and Ståhle, M. (2009) The Human Antimicrobial Peptide LL-37 Suppresses Apoptosis in Keratinocytes. Journal of Investigative Dermatology, 129, 937-944.
http://dx.doi.org/10.1038/jid.2008.321
[9] Koczulla, A.R. and Bals, R. (2003) Antimicrobial Peptides-Current Status and Therapeutics Potential. Drugs, 63, 389-406.
http://dx.doi.org/10.2165/00003495-200363040-00005
[10] Rosenfeld, Y. and Shai, Y. (2006) Lipopolysaccha-ride (Endotoxin)-Host Defense Antibacterial Peptides Interactions: Role in Bacterial Resistance and Prevention of Sepsis. BBA-Biomembranes, 1758, 1513-1522.
http://dx.doi.org/10.1016/j.bbamem.2006.05.017
[11] Suttmann, H., Retz, M., Paulsen, F., Harder, J., Zwergel, U., Kamradt, J., et al. (2008) Antimicrobial Peptides of the Cecropin-Family Show Potent Antitumor Activity Against Bladder Cancer Cells. BMC Urology, 8, 5.
http://dx.doi.org/10.1186/1471-2490-8-5
[12] Chan, S.C., Hui, L. and Chen, H.M. (1998) Enhancement of the Cytolytic Effect of Anti-Bacterial Cecropin by the Microvilli of Cancer Cells. Anticancer Research, 18, 4467-4474.
[13] Moore, A.J., Devine, D.A. and Bibby, M.C. (1994) Preliminary Experimental Anticancer Activity of Cecropins. Peptide Research, 7, 265-269.
[14] Chen, H.M., Wang, W., Smith, D. and Chan, S.C. (1997) Effects of the Anti-Bacterial Peptide Cecropin B and Its Analogs, Cecropins B-1 and B-2, on Liposomes, Bacteria, and Cancer Cells. Biochimica et Biophysica Acta, 1336, 171-179.
http://dx.doi.org/10.1016/S0304-4165(97)00024-X
[15] Sato, H. and Feix, J.B. (2006) Peptide-Membrane Interactions and Mechanisms of Membrane Destruction by Amphipathic α-Helical Antimicrobial Peptides. BBA, 9, 1245-1256.
http://dx.doi.org/10.1016/j.bbamem.2006.02.021
[16] Silvestro, L., Weiser, J.N. and Axelsen, P.H. (2000) Antibacterial and Antimembrane Activities of Cecropin A in Escherichia coli. Antimicrobial Agents and Chemotherapy, 44, 602-607.
http://dx.doi.org/10.1128/AAC.44.3.602-607.2000
[17] Jin, X.B., Mei, H.F., Li, X.B., Ma, Y., Zeng, A.H., Wang, Y., Lu, X., Chu, F., Wu, Q. and Zhu, J.Y. (2010) Apoptosis-Inducing Activity of the Antimicrobial Peptide Cecropin of Musca domestica in Human Hepatocelular Carcinoma Cell Line BEL-7402 and the Possible Mechanism. Acta Biochimica et Biophysica Sinica, 42, 259-265.
http://dx.doi.org/10.1093/abbs/gmq021
[18] Kourie, J.I. and Shorthouse, A.A. (2000) Properties of Cytotoxic Peptide-Formed Ion Channels. American Journal of Physiology. Cell Physiology, 278, C1063-C1087.
[19] Anghel, R., Jitaru, D., Badescu, L., Badescu, M. and Ciocoiu, M. (2013) The Cytotoxic Effect of Magainine II on the MDA-MB-231 and M14K Tumor Cell Lines. BioMed Research International, 2013, Article ID: 831709.
[20] Pascariu, M., Anghelache, N., Constantinescu, D., Jitaru, D., Carasevici, E. and Luchian, T. (2011) The Evaluation of Biological Effect of Cytotoxic Peptides on Tumor Cell Lines. Digest Journal of Nanomaterials and Biostructures, 7, 79-84.
[21] Masters, J.R. and Stacey, G.N. (2007) Changing Medium and Passaging Cell Lines. Nature Protocols, 2, 2276-2284.
http://dx.doi.org/10.1038/nprot.2007.319
[22] Ohno, T., Asakura, M., Awogi, T., Futamura,Y., Harihara, A., Hatao, M., Hayasaka, A. and Hayashi, M. (1998) Validation Study on Five Cytotoxicity Assays by JSAAE-VII. Details of the MTT Assay. Alternative Animal Test Experiment, 5, 1-38.
[23] Baas, P. (2002) Chemotherapy for Malignant Mesothelioma: From Doxorubicin to Vinorelbine. Seminars in Oncology, 29, 62-69.
http://dx.doi.org/10.1053/sonc.2002.30231
[24] Moskal, T.L., Urschel, J.D., Anderson, T.M., Antkowiak, J.G. and Takita, H. (1998) Malignant Pleural Mesothelioma: A Problematic Review. Surgical Oncology, 7, 5-12.
http://dx.doi.org/10.1016/S0960-7404(98)00019-X
[25] Adams, J.S., Ren, S., Liu, P.T., Chun, R.F., Lagishetty, V., Gombart, A.F., Borregaard, N., Modlin, R.L. and Hewison, M. (2009) Vitamin D-Directed Rheostatic Regulation of Monocyte Antibacterial Responses. Journal of Immunology, 182, 4289-4295.
http://dx.doi.org/10.4049/jimmunol.0803736
[26] Chromek, M., Slamová, Z., Bergman, P., Kovács, L., Podracká, L., Ehrén, I., Hökfelt, T., Gudmundsson, G.H., Gallo, R.L., Agerberth, B. and Brauner, A. (2006) The Antimicrobial Peptide Cathelicidin Protects the Urinary Tract against Invasive Bacterial Infection. Nature Medicine, 12, 636-641.
http://dx.doi.org/10.1038/nm1407
[27] Nizet, V., Ohtake, T., Lauth, X., Trowbridge, J., Rudisill, J., Dorschner, R.A., Pestonjamasp, V., Piraino, J., Huttner, K. and Gallo, R.L. (2001) Innate Antimicrobial Peptide Protects the Skin from Invasive Bacterial Infection. Nature, 414, 454-457.
http://dx.doi.org/10.1038/35106587
[28] Schauber, J., Dorschner, R.A., Yamasaki, K., Brouha, B. and Gallo, R.L. (2006) Control of the Innate Epithelial Anti-microbial Response Is Cell-Type Specific and Dependent on Relevant Microenvironmental Stimuli. Immunology, 118, 509-519.
[29] Brogden, K.A. (2005) Antimicrobial Peptides: Pore Formers or Metabolic Inhibitors in Bacteria? Nature Reviews Microbiology, 3, 238-250.
http://dx.doi.org/10.1038/nrmicro1098
[30] Cantor, R.S. (2002) Size Distribution of Barrel-Stave Aggregates of Membrane Peptides: Influence of the Bilayer Lateral Pressure Profile. Biophysical Journal, 82, 2520-2525.
http://dx.doi.org/10.1016/S0006-3495(02)75595-1
[31] Golec, M. (2007) Cathelicidin LL-37: LPS-Neutralizing, Pleiotropic Peptide. Annals of Agricultural and Environmental Medicine, 14, 1-4.
[32] Schmidtchen, A., Frick, I.M., Andersson, E., Tapper, H. and Björck, L. (2002) Proteinases of Common Pathogenic Bacteria Degrade and Inactivate the Antibacterial Peptide LL-37. Molecular Microbiology, 46, 157-168.
http://dx.doi.org/10.1046/j.1365-2958.2002.03146.x
[33] Sorensen, O.E., Follin, P., Johnsen, A.H., Calafat, J., Tjabringa, G.S., Hiemstra, P.S. and Borregaard, N. (2001) Human Cathelicidin, hCAP-18, Is Processed to the Antimicrobial Peptide LL-37 by Extracellular Cleavage with Proteinase 3. Blood, 97, 3951-3959.
http://dx.doi.org/10.1182/blood.V97.12.3951
[34] Yang, L., Harroun, T.A., Weiss, T.M., Ding, L. and Huang, H.W. (2001) Barrel-Stave Model or Toroidal Model? A Case Study on Melittin Pores. Biophysical Journal, 81, 1475-1485.
http://dx.doi.org/10.1016/S0006-3495(01)75802-X
[35] Dhople, V., Krukemeyer, A. and Ramamoorthy, A. (2006) The Human Beta-Defensin-3, an Antibacterial Peptide with Multiple Biological Functions. Biochimica et Biophysica Acta, 1758, 1499-1512.
http://dx.doi.org/10.1016/j.bbamem.2006.07.007
[36] Lee, D.K., Brender, J.R., Sciacca, M.F.M., Krishnamoorthy, J., Yu, C. and Ramamoorthy, A. (2013) Lipid Composition-Dependent Membrane Fragmentation and Pore-Forming Mechanisms of Membrane Disruption by Pexiganan (MSI-78). Biochemistry, 52, 3254-3263.
http://dx.doi.org/10.1021/bi400087n
[37] Ramamoorthy, A., Thennarasu, S., Lee, D.K., Tan, A. and Maloyy, L. (2006) Solid-State NMR Investigation of the Membrane-Disrupting Mechanism of Antimicrobial Peptides MSI-78 and MSI-594 Derived from Magainin 2 and Melittin. Biophysical Journal, 91, 206-216.
http://dx.doi.org/10.1529/biophysj.105.073890
[38] Ramamoorthy, A. (2009) Beyond NMR Spectra of Antimicrobial Peptides: Dynamical Images at Atomic Resolution and Functional Insights. Solid State Nuclear Magnetic Resonance, 35, 201-207.
http://dx.doi.org/10.1016/j.ssnmr.2009.03.003
[39] Thennarasu, S., Huang, R., Lee, D.K., Yang, P., Maloy, L., Chen, Z. and Ramamoorthy, A. (2010) Limiting an Antimicrobial Peptide to the Lipid-Water Interface Enhances Its Bacterial Membrane Selectivity: A Case Study of MSI-367. Biochemistry, 49, 10595-10605.
http://dx.doi.org/10.1021/bi101394r

  
comments powered by Disqus

Copyright © 2019 by authors and Scientific Research Publishing Inc.

Creative Commons License

This work and the related PDF file are licensed under a Creative Commons Attribution 4.0 International License.