Log in

The Anticancer Effect of a Conjugated Antimicrobial Peptide Against Colorectal Cancer (CRC) Cells

  • Original Research
  • Published:
Journal of Gastrointestinal Cancer Aims and scope Submit manuscript

Abstract

Purpose

Although antimicrobial peptides (AMPs) were initially known as compounds of the innate immune system to fight microbial pathogens, it has been recently proposed that differences in normal and cancer cell membranes cause the anticancer effect of these peptides. The aim of this study was to evaluate the anticancer effect of MELITININ+BMAP27-conjugated peptide against colorectal cancer (CRC) cells.

Methods

The MELITININ+BMAP27-conjugated peptides were designed and the β-naphthylalanine residues were added to the termini to improve the anticancer effect. CRC cancer cell lines including HT29, SW742, HCT-116, and WiDr were used. After preparing concentrations of 5, 10, 25, 50, 100, 150, 200, and 400 μg/mL of peptide solution, the rate of cell death after 12, 24, and 48 h was assessed using MTT test. After confirmation of the 30 µg/mL efficacy and nontoxic concentration, the cells were exposed to this concentration, and the total RNA was extracted. The quantitative real-time PCR (RT-qPCR) technique was performed for the amplification of Bax, caspase3, atg5, and GAPDH (glyceraldehyde 3-phosphate dehydrogenase as the internal control) genes.

Results

The cytotoxicity of peptide against normal cells exhibited that the IC50 at 24 and 4 h included 80 and 100 µg/mL, respectively. After 24–72 h of treatment, a significant difference in the mean percentage of CRC living cells was observed at concentrations of 50–400 μg/mL of conjugated peptide (p < 0.05). The IC50 of the peptide at 24, 48, and 72 h of exposure was measured as 30, 20, and 10 μg/mL, respectively. The peptide resulted in a significant increase of 2.35-fold in the mean expression of Bax gene in CRC cells (p < 0.001). It also caused a significant increase of 1.75 times (p = 0.0112) of caspase 3 gene and 1.2 times (p = 0.0217) of atg5 gene. There was no significant difference among cell lines regarding the expression of each gene.

Conclusion

The conjugated peptide caused the death of CRC lines via induction of the apoptosis and necrosis mechanisms. More studies are needed in this regard.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Subscribe and save

Springer+ Basic
EUR 32.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or Ebook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7

Similar content being viewed by others

Availability of Data and Materials

All the data generated or analyzed during this study are included in this published article (and its supplementary information files).

References

  1. Okamoto R, Gery S, Kuwayama Y, Borregaard N, Ho Q, Alvarez R, Akagi T, Liu GY, Uskokovic MR, Koeffler HP. Novel Gemini vitamin D3 analogs: large structure/function analysis and ability to induce antimicrobial peptide. Int J Cancer. 2014;134(1):207–17.

    Article  PubMed  Google Scholar 

  2. Torrisi M, Pollastri G, Le Q. Deep learning methods in protein structure prediction. Comput Struct Biotechnol J. 2020;18:1301–10.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Liu X, Li Y, Li Z, Lan X, Leung PH, Li J, Yang M, Ko F, Qin L. Mechanism of anticancer effects of antimicrobial peptides. Journal of Fiber Bioengineering and Informatics. 2015;8(1):25–36.

    Article  Google Scholar 

  4. Hoskin DW, Ramamoorthy A. Studies on anticancer activities of antimicrobial peptides. Biochimica et Biophysica Acta (BBA)-Biomembranes. 2008;1778(2):357–75.

  5. Yu G, Baeder DY, Regoes RR, Rolff J. Combination effects of antimicrobial peptides. Antimicrob Agents Chemother. 2016;60(3):1717–24.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Chu HL, Yip BS, Chen KH, Yu HY, Chih YH, Cheng HT, Chou YT, Cheng JW. Novel antimicrobial peptides with high anticancer activity and selectivity. PLoS One. 2015;10(5):e0126390.

  7. Zandsalimi F, Talaei S, Noormohammad Ahari M, Aghamiri S, Raee P, Roshanzamiri S, Yarian F, Bandehpour M, Zohrab ZZ. Antimicrobial peptides: a promising strategy for lung cancer drug discovery? Expert Opin Drug Discov. 2020;15(11):1343–54.

    Article  CAS  PubMed  Google Scholar 

  8. Tornesello AL, Borrelli A, Buonaguro L, Buonaguro FM, Tornesello ML. Antimicrobial peptides as anticancer agents: functional properties and biological activities. Molecules. 2020;25(12):2850.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Leite ML, da Cunha NB, Costa FF. Antimicrobial peptides, nanotechnology, and natural metabolites as novel approaches for cancer treatment. Pharmacol Ther. 2018;1(183):160–76.

    Article  Google Scholar 

  10. Joseph L, Srinivasan K. Triacontanoic ester of 5ʹʹ-hydroxyjustisolin: Tumour suppressive role in cervical cancer via Bcl-2, BAX and caspase-3 mediated signalling. Toxicol Rep. 2019;6:1198–205.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Yue Y, Lv W, Zhang L, Kang W. MiR-147b influences vascular smooth muscle cell proliferation and migration via targeting YY1 and modulating Wnt/β-catenin activities. Acta Biochim Biophys Sin. 2018;50:905–13.

    Article  CAS  PubMed  Google Scholar 

  12. Hamdan NT, Jwad BAAAA, Jasim SA. Synergistic anticancer effects of phycocyanin and Citrullus colocynthis extract against WiDr, HCT-15 and HCT-116 colon cancer cell lines. Gene Rep. 2021;22:100972.

  13. Baxter AA, Lay FT, Poon IK, Kvansakul M, Hulett MD. Tumor cell membrane-targeting cationic antimicrobial peptides: novel insights into mechanisms of action and therapeutic prospects. Cell Mol Life Sci. 2017;74(20):3809–25.

    Article  CAS  PubMed  Google Scholar 

  14. Moore KS, Bevins CL, Brasseur MM, Tomassini N, Turner K, Eck H, Zasloff M. Antimicrobial peptides in the stomach of Xenopus laevis. J Biol Chem. 1991;266:19851–7.

    Article  CAS  PubMed  Google Scholar 

  15. Hilchie AL, Hoskin DW, Coombs MP. Anticancer activities of natural and synthetic peptides. Antimicrob Peptides. 2019:131–47.

  16. Emelianova AA, Kuzmin DV, Panteleev PV, Sorokin M, Buzdin AA, Ovchinnikova TV. Anticancer activity of the goat antimicrobial peptide ChMAP-28. Front Pharmacol. 2018;21(9):1501.

    Article  Google Scholar 

  17. Wang C, Dong S, Zhang L, Zhao Y, Huang L, Gong X, Wang H, Shang D. Cell surface binding, uptaking and anticancer activity of L-K6, a lysine/leucine-rich peptide, on human breast cancer MCF-7 cells. Sci Rep. 2017;7(1):1–3.

    PubMed  PubMed Central  Google Scholar 

  18. Pedron CN, Andrade GP, Sato RH, Torres MD, Cerchiaro G, Ribeiro AO, Oliveira VX Jr. Anticancer activity of VmCT1 analogs against MCF-7 cells. Chem Biol Drug Des. 2018;91(2):588–96.

    Article  CAS  PubMed  Google Scholar 

  19. Deslouches B, Di YP. Antimicrobial peptides with selective antitumor mechanisms: prospect for anticancer applications. Oncotarget. 2017;8(28):46635.

    Article  PubMed  PubMed Central  Google Scholar 

  20. Araki M, Kurihara M, Kinoshita S, Awane R, Sato T, Ohkawa Y, Inoue YH. Anti-tumour effects of antimicrobial peptides, components of the innate immune system, against haematopoietic tumours in Drosophila mxc mutants. Dis Models Mech. 2019;12(6):dmm037721.

Download references

Acknowledgements

This study was performed by the authors.

Funding

This study was supported by Al-Maarif University College, Iraq.

Author information

Authors and Affiliations

Authors

Contributions

All the authors have participated equally.

Corresponding author

Correspondence to Saade Abdalkareem Jasim.

Ethics declarations

Ethics Approval and Consent to Participate

This study was approved by the ethics committee of Al-maarif University. All the authors had the written consent to participate (those subjects without the consent had been excluded from the study).

Consent for Publication

All the authors have the consent of publication. Moreover, the patients have the consent of participation and publication.

Competing Interests

The authors declare no competing interests.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Saleh, R.O., Essia, I.N.A. & Jasim, S.A. The Anticancer Effect of a Conjugated Antimicrobial Peptide Against Colorectal Cancer (CRC) Cells. J Gastrointest Canc 54, 165–170 (2023). https://doi.org/10.1007/s12029-021-00799-4

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12029-021-00799-4

Keywords

Navigation