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Anticancer Effect of Enterocin A-Colicin E1 Fusion Peptide on the Gastric Cancer Cell

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Abstract

Cancer is one of the most causes of death all over the world, although improvements in its treatment and recognition. Due to the limitations of common anticancer methods, including surgery, chemotherapy, and radiotherapy, attention has been drawn to other anti-cancer compounds, especially natural peptides such as bacteriocins. In this study, we used a combination of two bacteriocins, colicin E1 and enterocin A, against AGS gastric cancer cell lines. In order to evaluate anticancer properties of fusion peptide, we applied MTT assay, real-time PCR, and flow cytometry tests. This is the first report to show the cell growth inhibitory activity of the enterocin A in combination with colicin E1 against AGS human cancer cells. The results of this study showed that this fusion peptide at a concentration of 60.4 µg/mL and 24 h was able to kill half of the tested cancer cells, and treatment of the cells with this concentration increased the expression of bax and caspase 3 genes and reduced the expression of bacl-2 in 24 h. Flow cytometry analysis of annexin V-FITC/propidium iodide results also showed that our peptide was able to induce apoptosis in treated cells compared with control. Taken together, enterocin A-colicin E1 (ent A-col E1) can be considered as a good candidate for anticancer therapies.

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All data analyzed during this study are included in this published article.

References

  1. Jamali L, Tofigh R, Tutunchi S, Panahi G, Borhani F, Akhavan S, Nourmohammadi P, Ghaderian SMH, Rasouli M, Mirzaei H (2018) Circulating microRNAs as diagnostic and therapeutic biomarkers in gastric and esophageal cancers. J Cell Physiol 233(11):8538–8550. https://doi.org/10.1002/jcp.26850

    Article  CAS  PubMed  Google Scholar 

  2. Simonian M, Mosallayi M, Mirzaei H (2018) Circulating miR-21 as a novel biomarker in gastric cancer: diagnostic and prognostic biomarker. J Cancer Res Ther 14(2):475. https://doi.org/10.4103/0973-1482.175428

    Article  CAS  PubMed  Google Scholar 

  3. Faghihloo E, Araei Y, Mohammadi M, Mirzaei H, Mohammadi HR, Mokhtari-Azad T (2016) The effect of oxamflatin on the E-cadherin expression in the gastric cancer cell line. Cancer Gene Ther 23(11):396–399. https://doi.org/10.1038/cgt.2016.52

    Article  CAS  PubMed  Google Scholar 

  4. Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D (2011) Global cancer statistics. CA Cancer J Clin 61(2):69–90. https://doi.org/10.3322/caac.21492

    Article  PubMed  Google Scholar 

  5. Li C, Tian ZN, Cai JP, Chen KX, Zhang B, Feng MY, Shi QT, Li R, Qin Y, Geng JS (2014) Panax ginseng polysaccharide induces apoptosis by targeting Twist/AKR1C2/NF-1 pathway in human gastric cancer. Carbohydr Polym 102:103–109. https://doi.org/10.1016/j.carbpol.2013.11.016

    Article  CAS  PubMed  Google Scholar 

  6. Park HS, Hong NR, Ahn TS, Kim H, Jung MH, Kim BJ (2015) Apoptosis of AGS human gastric adenocarcinoma cells by methanolic extract of dictamnus. Pharmacogn Mag 11(Suppl 2):S329-336. https://doi.org/10.4103/0973-1296.165994

    PubMed  PubMed Central  Google Scholar 

  7. Mirzaei H, Sahebkar A, Avan A, Jaafari MR, Salehi R, Salehi H, Baharvand H, Rezaei A, Hadjati J, Pawelek JM, Mirzaei HR (2016) Application of mesenchymal stem cells in melanoma: a potential therapeutic strategy for delivery of targeted agents. Curr Med Chem 23(5):455–463. https://doi.org/10.2174/0929867323666151217122033

    Article  CAS  PubMed  Google Scholar 

  8. Mohammadi M, Jaafari MR, Mirzaei HR, Mirzaei H (2016) Mesenchymal stem cell: a new horizon in cancer gene therapy. Cancer Gene Ther 23(9):285–286. https://doi.org/10.1038/cgt.2016.35

    Article  CAS  PubMed  Google Scholar 

  9. Kaur S, Kaur S (2015) Bacteriocins as potential anticancer agents. Front Pharmacol 6:272. https://doi.org/10.3389/fphar.2015.00272

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Arunmanee W, Ecoy GAU, Khine HEE, Duangkaew M, Prompetchara E, Chanvorachote P, Chaotham C (2020) Colicin N mediates apoptosis and suppresses integrin-modulated survival in human lung cancer cells. Molecules 25(4). https://doi.org/10.3390/molecules25040816

  11. Wang SM, Zhang LW, Fan RB, Han X, Yi HX, Zhang LL, Xue CH, Li HB, Zhang YH, Shigwedha N (2014) Induction of HT-29 cells apoptosis by lactobacilli isolated from fermented products. Res Microbiol 165(3):202–214. https://doi.org/10.1016/j.resmic.2014.02.004

    Article  CAS  PubMed  Google Scholar 

  12. Nami Y, Abdullah N, Haghshenas B, Radiah D, Rosli R, Yari Khosroushahi A (2014) A newly isolated probiotic Enterococcus faecalis strain from vagina microbiota enhances apoptosis of human cancer cells. J Appl Microbiol 117(2):498–508. https://doi.org/10.1111/jam.12531

    Article  CAS  PubMed  Google Scholar 

  13. Ankaiah D, Esakkiraj P, Perumal V, Ayyanna R, Venkatesan A (2017) Probiotic characterization of Enterococcus faecium por1: cloning, overexpression of enterocin-A and evaluation of antibacterial, anti-cancer properties. J Funct Foods 38:280–292. https://doi.org/10.1016/j.jff.2017.09.034

    Article  CAS  Google Scholar 

  14. Kumar B, Balgir P, Kaur B, Mittu B, Chauhan A (2012) In vitro cytotoxicity of native and rec-pediocin CP2 against cancer cell lines: a comparative study. Pharm Anal Acta 1(6). https://doi.org/10.4172/2153-2435.1000183

  15. Ankaiah D, Palanichamy E, Antonyraj CB, Ayyanna R, Perumal V, Ahamed SIB, Arul V (2018) Cloning, overexpression, purification of bacteriocin enterocin-B and structural analysis, interaction determination of enterocin-A, B against pathogenic bacteria and human cancer cells. Int J Biol Macromol 116:502–512. https://doi.org/10.1016/j.ijbiomac.2018.05.002

    Article  CAS  PubMed  Google Scholar 

  16. Hoskin DW, Ramamoorthy A (2008) Studies on anticancer activities of antimicrobial peptides. Biochim Biophys Acta 1778(2):357–375. https://doi.org/10.1016/j.bbamem.2007.11.008

    Article  CAS  PubMed  Google Scholar 

  17. Chan S-C, Hui L, Chen HM (1998) Enhancement of the cytolytic effect of anti-bacterial cecropin by the microvilli of cancer cells. Anticancer Res 18(6A):4467–4474

    CAS  PubMed  Google Scholar 

  18. Sok M, Šentjurc M, Schara M (1999) Membrane fluidity characteristics of human lung cancer. Cancer Lett 139(2):215–220. https://doi.org/10.1016/S0304-3835(99)00044-0

    Article  CAS  PubMed  Google Scholar 

  19. Bhutia SK, Maiti TK (2008) Targeting tumors with peptides from natural sources. Trends Biotechnol 26(4):210–217. https://doi.org/10.1016/j.tibtech.2008.01.002

    Article  CAS  PubMed  Google Scholar 

  20. Chumchalova J, Šmarda J (2003) Human tumor cells are selectively inhibited by colicins. Folia Microbiol (Praha) 48(1):111–115. https://doi.org/10.1007/BF02931286

    Article  CAS  Google Scholar 

  21. Smarda J, Fialova M, Smarda J Jr (2001) Cytotoxic effects of colicins E1 and E3 on v-myb-transformed chicken monoblasts. Folia Biol (Praha) 47(1):11–13

    CAS  Google Scholar 

  22. Šmarda J, Obdržálek V, Táborský I, Mach J (1978) The cytotoxic and cytocidal effect of colicin E3 on mammalian tissue cells. Folia Microbiol (Praha) 23(4):272–277. https://doi.org/10.1007/BF02876680

    Article  Google Scholar 

  23. Konings WN, Kok J, Kuipers OP, Poolman B (2000) Lactic acid bacteria: the bugs of the new millennium. Curr Opin Microbiol 3(3):276–282. https://doi.org/10.1016/S1369-5274(00)00089-8

    Article  CAS  PubMed  Google Scholar 

  24. Satish Kumar R, Kanmani P, Yuvaraj N, Paari KA, Pattukumar V, Arul V (2011) Purification and characterization of enterocin MC13 produced by a potential aquaculture probiont Enterococcus faecium MC13 isolated from the gut of Mugil cephalus. Can J Microbiol 57(12):993–1001. https://doi.org/10.1139/w11-092

    Article  CAS  PubMed  Google Scholar 

  25. Helmerhorst EJ, Reijnders IM, van’t Hof W, Veerman EC, Nieuw Amerongen AV (1999) A critical comparison of the hemolytic and fungicidal activities of cationic antimicrobial peptides. FEBS Lett 449(2–3):105–110. https://doi.org/10.1016/S0014-5793(99)00411-1

    Article  CAS  PubMed  Google Scholar 

  26. Pirkhezranian Z, Tanhaeian A, Mirzaii M, Sekhavati MH (2019) Expression of enterocin-P in HEK platform: evaluation of its cytotoxic effects on cancer cell lines and its potency to interact with cell-surface glycosaminoglycan by molecular modeling. Int J Pept Res Ther 26:1503–1512. https://doi.org/10.1007/s10989-019-09956-7

    Article  CAS  Google Scholar 

  27. Haghshenas B, Abdullah N, Nami Y, Radiah D, Rosli R, Khosroushahi AY (2014) Different effects of two newly-isolated probiotic Lactobacillus plantarum 15HN and Lactococcus lactis subsp. Lactis 44Lac strains from traditional dairy products on cancer cell lines. Anaerobe 30:51–59. https://doi.org/10.1016/j.anaerobe.2014.08.009

    Article  CAS  PubMed  Google Scholar 

  28. Fathizadeh H, Saffari M, Esmaeili D, Moniri R, Salimian M (2020) Evaluation of the antibacterial activity of enterocin A-colicin E1 fusion peptide. Iran J Basic Med Sci 23 (11):1471-1479. https://doi.org/10.22038/ijbms.2020.47826.11004

  29. Ferlay J, Soerjomataram I, Dikshit R, Eser S, Mathers C, Rebelo M, Parkin DM, Forman D, Bray F (2015) Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer 136(5):E359–E386. https://doi.org/10.1002/ijc.29210

    Article  CAS  PubMed  Google Scholar 

  30. Chumchalova J, Smarda J (2003) Human tumor cells are selectively inhibited by colicins. Folia Microbiol (Praha) 48(1):111–115. https://doi.org/10.1007/BF02931286

    Article  CAS  Google Scholar 

  31. Villarante KI, Elegado FB, Iwatani S, Zendo T, Sonomoto K, de Guzman EE (2011) Purification, characterization and in vitro cytotoxicityof the bacteriocin from Pediococcus acidilactici K2a2-3 againsthuman colon adenocarcinoma (HT29) and human cervicalcarcinoma (HeLa) cells. World J Microbiol Biotechnol 27(4):975–80. https://doi.org/10.1007/s11274-010-0541-1

    Article  CAS  Google Scholar 

  32. Hetz C, Bono MR, Barros LF, Lagos R (2002) Microcin E492, a channel-forming bacteriocin from Klebsiella pneumoniae, induces apoptosis in some human cell lines. Proc Natl Acad Sci 99(5):2696–2701. https://doi.org/10.1073/pnas.052709699

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Abdi-Ali A, Worobec E, Deezagi A, Malekzadeh F (2004) Cytotoxic effects of pyocin S2 produced by Pseudomonas aeruginosa on the growth of three human cell lines. Can J Microbiol 50(5):375–381. https://doi.org/10.1139/w04-019

    Article  CAS  PubMed  Google Scholar 

  34. Berridge MV, Herst PM, Tan AS (2005) Tetrazolium dyes as tools in cell biology: new insights into their cellular reduction. Biotechnol Annu Rev 11:127–152. https://doi.org/10.1016/s1387-2656(05)11004-7

    Article  CAS  PubMed  Google Scholar 

  35. Paiva AD, de Oliveira MD, de Paula SO, Baracat-Pereira MC, Breukink E, Mantovani HC (2012) Toxicity of bovicin HC5 against mammalian cell lines and the role of cholesterol in bacteriocin activity. Microbiology (Reading) 158(Pt 11):2851–2858. https://doi.org/10.1099/mic.0.062190-0

    Article  CAS  Google Scholar 

  36. Fuska J, Fusková A, Šmarda J, Mach J (1979) Effect of colicin E3 on leukemia cells P 388 in vitro. Experientia 35(3):406–407. https://doi.org/10.1007/BF01964380

    Article  CAS  PubMed  Google Scholar 

  37. Vandesompele J, De Preter K, Pattyn F, Poppe B, Van Roy N, De Paepe A, Speleman F (2002) Accurate normalization of real-time quantitative RT-PCR data by geometric averaging of multiple internal control genes. Genome Biol 3 (7): Research0034. https://doi.org/10.1186/gb-2002-3-7-research0034

  38. Mitselou A, Ioachim E, Kitsou E, Vougiouklakis T, Zagorianakou N, Makrydimas G, Stefanaki S, Agnantis N (2003) Immunohistochemical study of apoptosis-related Bcl-2 protein and its correlation with proliferation indices (Ki67, PCNA), tumor suppressor genes (p53, pRb), the oncogene c-erbB-2, sex steroid hormone receptors, and other clinicopathological features, in normal, hyperplastic and neoplastic endometrium. vivo 17(5):469–477

    CAS  Google Scholar 

  39. Hockenbery D, Nuñez G, Milliman C, Schreiber RD, Korsmeyer SJ (1990) Bcl-2 is an inner mitochondrial membrane protein that blocks programmed cell death. Nature 348(6299):334–336. https://doi.org/10.1038/348334a0

    Article  CAS  PubMed  Google Scholar 

  40. Sakuragi N, Salah-eldin AE, Watari H, Itoh T, Inoue S, Moriuchi T, Fujimoto S (2002) Bax, Bcl-2, and p53 expression in endometrial cancer. Gynecol Oncol 86(3):288–296. https://doi.org/10.1006/gyno.2002.6742

    Article  CAS  PubMed  Google Scholar 

  41. Wyllie AH (1997) Apoptosis: an overview. Br Med Bull 53(3):451–465. https://doi.org/10.1093/oxfordjournals.bmb.a011623

    Article  CAS  PubMed  Google Scholar 

  42. Ahmadi S, Ghollasi M, Hosseini HM (2017) The apoptotic impact of nisin as a potent bacteriocin on the colon cancer cells. Microb Pathog 111:193–197. https://doi.org/10.1016/j.micpath.2017.08.037

    Article  CAS  PubMed  Google Scholar 

  43. Kamarajan P, Hayami T, Matte B, Liu Y, Danciu T, Ramamoorthy A, Worden F, Kapila S, Kapila Y (2015) Nisin ZP, a bacteriocin and food preservative, inhibits head and neck cancer tumorigenesis and prolongs survival. PLoS One 10(7):e0131008. https://doi.org/10.1371/journal.pone.0131008

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Rastin M, Hatef MR, Tabasi N, Mahmoudi M (2012) The pathway of estradiol-induced apoptosis in patients with systemic lupus erythematosus. Clin Rheumatol 31(3):417–424. https://doi.org/10.1007/s10067-011-1821-3

    Article  PubMed  Google Scholar 

  45. Elmore S (2007) Apoptosis: a review of programmed cell death. Toxicol Pathol 35(4):495–516. https://doi.org/10.1080/01926230701320337

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Koopman G, Reutelingsperger CP, Kuijten GA, Keehnen RM, Pals ST, van Oers MH (1994) Annexin V for flow cytometric detection of phosphatidylserine expression on B cells undergoing apoptosis. Blood 84(5):1415–1420

    Article  CAS  PubMed  Google Scholar 

  47. Arunmanee W, Ecoy GAU, Khine HEE, Duangkaew M, Prompetchara E, Chanvorachote P, Chaotham C (2020) Colicin N mediates apoptosis and suppresses integrin-modulated survival in human lung cancer cells. Molecules 25(4):816. https://doi.org/10.3390/molecules25040816

    Article  CAS  PubMed Central  Google Scholar 

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Funding

This research was supported by the Kashan University of Medical Sciences (Grant no. 97149).

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HF and DE designed and performed experiments and analyzed data. HF and MS wrote the manuscript with support from RM, MS, and JM.

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Correspondence to Mahmood Saffari or Davoud Esmaeili.

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Fathizadeh, H., Saffari, M., Esmaeili, D. et al. Anticancer Effect of Enterocin A-Colicin E1 Fusion Peptide on the Gastric Cancer Cell. Probiotics & Antimicro. Prot. 13, 1443–1451 (2021). https://doi.org/10.1007/s12602-021-09770-y

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