Skip to content
2000
Volume 26, Issue 7
  • ISSN: 1389-2037
  • E-ISSN: 1875-5550

Abstract

Background

Colorectal cancer (CRC) is one of the most common malignancies worldwide, and despite advances in treatment, there remains a critical need for novel therapeutic approaches. Recently, anti-microbial peptides (AMPs) have gained attention for their potential use in cancer therapy due to their selective cytotoxicity towards cancer cells.

Objective

This study aims to evaluate the anti-cancer potential of two computationally engineered anti-microbial peptides (EAMPs) in SW620, SW480, and HCT116 colon cancer cells and the normal colon epithelial cell line CCD 841, focusing on their effects on cell proliferation, apoptosis, and DNA damage.

Methods

Cell proliferation and survival were measured using the CellTiter-Glo Luminescence and clonogenic assays. DNA damage was assessed through the Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay. Flow cytometry was used to examine cell apoptosis, cell cycle distribution, and mitochondrial membrane potential in SW620 cells.

Results

EAMPs inhibited CRC cell proliferation in a dose-dependent manner, with minimal toxicity observed in normal colon epithelial cells. In SW620 cells, EAMPs induced DNA damage, resulting in cell cycle arrest at the S/G2 phase, apoptosis, and a reduction in mitochondrial membrane potential. The proliferation results were confirmed in SW480 and HCT116 CRC cell lines.

Conclusion

Our findings revealed that EAMPs exhibited significant anti-cancer activity against CRC cells while sparing normal epithelial cells. These results suggest that EAMPs may offer a potential therapeutic approach for colorectal cancer and warrant further investigation.

Loading

Article metrics loading...

/content/journals/cpps/10.2174/0113892037363898250110053529
2025-02-11
2025-09-17
Loading full text...

Full text loading...

References

  1. SungH. FerlayJ. SiegelR.L. LaversanneM. SoerjomataramI. JemalA. BrayF. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries.CA Cancer J. Clin.202171320924910.3322/caac.2166033538338
    [Google Scholar]
  2. MorganE. ArnoldM. GiniA. LorenzoniV. CabasagC.J. LaversanneM. VignatJ. FerlayJ. MurphyN. BrayF. Global burden of colorectal cancer in 2020 and 2040: Incidence and mortality estimates from GLOBOCAN.Gut202372233834410.1136/gutjnl‑2022‑32773636604116
    [Google Scholar]
  3. BrennerD.R. HeerE. SutherlandR.L. RuanY. TinmouthJ. HeitmanS.J. HilsdenR.J. National trends in colorectal cancer incidence among older and younger adults in Canada.JAMA Netw. Open201927e19809010.1001/jamanetworkopen.2019.809031365108
    [Google Scholar]
  4. XiY. XuP. Global colorectal cancer burden in 2020 and projections to 2040.Transl. Oncol.2021141010117410.1016/j.tranon.2021.10117434243011
    [Google Scholar]
  5. MyerP.A. LeeJ.K. MadisonR.W. PradhanK. NewbergJ.Y. IsasiC.R. KlempnerS.J. FramptonG.M. RossJ.S. VenstromJ.M. SchrockA.B. DasS. AugenlichtL. VermaA. GreallyJ.M. RajS.M. GoelS. AliS.M. The genomics of colorectal cancer in populations with African and European ancestry.Cancer Discov.20221251282129310.1158/2159‑8290.CD‑21‑081335176763
    [Google Scholar]
  6. Sousa-SquiavinatoA.C.M. Arregui RamosD.A. WagnerM.S. TessmannJ.W. de-Freitas-JuniorJ.C.M. Morgado-DíazJ.A. Long-term resistance to 5-fluorouracil promotes epithelial–mesenchymal transition, apoptosis evasion, autophagy, and reduced proliferation rate in colon cancer cells.Eur. J. Pharmacol.202293317525310.1016/j.ejphar.2022.17525336067803
    [Google Scholar]
  7. ZhaoZ. YangY. LiuW. LiZ. T59, a new compound reconstructed from curcumin, induces cell apoptosis through reactive oxygen species activation in human lung cancer cells.Molecules2018236125110.3390/molecules2306125129882920
    [Google Scholar]
  8. EngC. RogersJ.E. Current synthetic pharmacotherapy for treatment-resistant colorectal cancer: When urgent action is required.Expert Opin. Pharmacother.201920552353410.1080/14656566.2018.156186630590946
    [Google Scholar]
  9. Hernandez DominguezO. YilmazS. SteeleS.R. Stage IV colorectal cancer management and treatment.J. Clin. Med.2023125207210.3390/jcm1205207236902858
    [Google Scholar]
  10. GattiL. ZuninoF. Overview of tumor cell chemoresistance mechanisms.Methods Mol. Med.200511112714815911977
    [Google Scholar]
  11. Al BitarS. El-SabbanM. DoughanS. Abou-KheirW. Molecular mechanisms targeting drug-resistance and metastasis in colorectal cancer: Updates and beyond.World J. Gastroenterol.20232991395142610.3748/wjg.v29.i9.139536998426
    [Google Scholar]
  12. Fares AmerN. Luzzatto KnaanT. Natural products of marine origin for the treatment of colorectal and pancreatic cancers: Mechanisms and potential.Int. J. Mol. Sci.20222314804810.3390/ijms2314804835887399
    [Google Scholar]
  13. BaindaraP. MandalS.M. Bacteria and bacterial anticancer agents as a promising alternative for cancer therapeutics.Biochimie202017716418910.1016/j.biochi.2020.07.02032827604
    [Google Scholar]
  14. ChauhanS. DhawanD.K. SainiA. PreetS. Antimicrobial peptides against colorectal cancer-a focused review.Pharmacol. Res.202116710552910.1016/j.phrs.2021.10552933675962
    [Google Scholar]
  15. YeG. WuH. HuangJ. WangW. GeK. LiG. ZhongJ. HuangQ. LAMP2: A major update of the database linking antimicrobial peptides.Database (Oxford)20202020baaa06110.1093/database/baaa06132844169
    [Google Scholar]
  16. ZupinL. Santos-SilvaC.A. Al MughrbiA.R.H. VilelaL.M.B. Benko-IsepponA.M. CrovellaS. Bioactive anti-microbial peptides: A new weapon to counteract zoonosis.Microorganisms2022108159110.3390/microorganisms1008159136014009
    [Google Scholar]
  17. ThapaR.K. DiepD.B. TønnesenH.H. Topical antimicrobial peptide formulations for wound healing: Current developments and future prospects.Acta Biomater.2020103526710.1016/j.actbio.2019.12.02531874224
    [Google Scholar]
  18. HaneyE.F. MansourS.C. HilchieA.L. de la Fuente-NúñezC. HancockR.E.W. High throughput screening methods for assessing antibiofilm and immunomodulatory activities of synthetic peptides.Peptides20157127628510.1016/j.peptides.2015.03.01525836992
    [Google Scholar]
  19. LuF. ZhuY. ZhangG. LiuZ. Renovation as innovation: Repurposing human antibacterial peptide LL-37 for cancer therapy.Front. Pharmacol.20221394414710.3389/fphar.2022.94414736081952
    [Google Scholar]
  20. SalehR.O. EssiaI.N.A. JasimS.A. The anti-cancer effect of a conjugated anti-microbial peptide against colorectal cancer (CRC) cells.J. Gastrointest. Cancer202354116517010.1007/s12029‑021‑00799‑435217999
    [Google Scholar]
  21. WeiP.L. LinJ.C. HungC.S. MakondiP.T. BatzorigU. ChangT.C. HuangC.Y. ChangY.J. Human α-defensin 6 (HD6) suppresses CRC proliferation and metastasis through abolished EGF/EGFR signaling pathway.Int. J. Med. Sci.2022191344610.7150/ijms.6485034975297
    [Google Scholar]
  22. JafariA. BabajaniA. Sarrami ForooshaniR. YazdaniM. Rezaei-TaviraniM. Clinical applications and anti-cancer effects of anti-microbial peptides: From bench to bedside.Front. Oncol.20221281956310.3389/fonc.2022.81956335280755
    [Google Scholar]
  23. Avilés-GaxiolaS. Gutiérrez-GrijalvaE.P. León-FelixJ. Angulo-EscalanteM.A. HerediaJ.B. Peptides in colorectal cancer: Current state of knowledge.Plant Foods Hum. Nutr.202075446747610.1007/s11130‑020‑00856‑632964320
    [Google Scholar]
  24. MaijaroenS. KlaynongsruangS. RoytrakulS. KonkchaiyaphumM. TaemaitreeL. JangprommaN. An integrated proteomics and bioinformatics analysis of the anti-cancer properties of RT2 anti-microbial peptide on human colon cancer (Caco-2) cells.Molecules2022274142610.3390/molecules2704142635209215
    [Google Scholar]
  25. Al KashgryN.A.T. AbulreeshH.H. El-SheikhI.A. AlmaroaiY.A. SalemR. MohamedI. WalyF.R. OsmanG. MohamedM.S.M. Utilization of a recombinant defensin from Maize (Zea mays L.) as a potential antimicrobial peptide.AMB Express202010120810.1186/s13568‑020‑01146‑933237335
    [Google Scholar]
  26. González-MontielG.A. KaweesaE.N. FeauN. HamelinR.C. StoneJ.K. LoesgenS. Chemical, bioactivity, and biosynthetic screening of epiphytic fungus Zasmidium pseudotsugae.Molecules20202510235810.3390/molecules2510235832438585
    [Google Scholar]
  27. WaghuF.H. Idicula-ThomasS. Collection of antimicrobial peptides database and its derivatives: Applications and beyond.Protein Sci.2020291364210.1002/pro.371431441165
    [Google Scholar]
  28. ZhangK. TengD. MaoR. YangN. HaoY. WangJ. Thinking on the construction of anti-microbial peptide databases: Powerful tools for the molecular design and screening.Int. J. Mol. Sci.2023244313410.3390/ijms2404313436834553
    [Google Scholar]
  29. UniProt Consortium UniProt: a worldwide hub of protein knowledge.Nucleic Acids Res.201947D1D506D51510.1093/nar/gky104930395287
    [Google Scholar]
  30. SieversF. WilmA. DineenD. GibsonT.J. KarplusK. LiW. LopezR. McWilliamH. RemmertM. SödingJ. ThompsonJ.D. HigginsD.G. Fast, scalable generation of high-quality protein multiple sequence alignments using Clustal Omega.Mol. Syst. Biol.20117153910.1038/msb.2011.7521988835
    [Google Scholar]
  31. BeaufilsC. HernandezJ.F. RodriguezM. Rational design of antimicrobial peptides: Current advances and limitations.Appl. Microbiol. Biotechnol.201296613811395
    [Google Scholar]
  32. AbrahamM.J. MurtolaT. SchulzR. PállS. SmithJ.C. HessB. LindahlE. GROMACS: High performance molecular simulations through multi-level parallelism from laptops to supercomputers.SoftwareX20151-2192510.1016/j.softx.2015.06.001
    [Google Scholar]
  33. BerendsenH.J.C. van der SpoelD. van DrunenR. GROMACS: A message-passing parallel molecular dynamics implementation.Comput. Phys. Commun.1995911-3435610.1016/0010‑4655(95)00042‑E
    [Google Scholar]
  34. OostenbrinkC. SoaresT.A. van der VegtN.F.A. van GunsterenW.F. Validation of the 53A6 GROMOS force field.Eur. Biophys. J.200534427328410.1007/s00249‑004‑0448‑615803330
    [Google Scholar]
  35. MuttenthalerM. KingG.F. AdamsD.J. AlewoodP.F. Trends in peptide drug discovery.Nat. Rev. Drug Discov.202120430932510.1038/s41573‑020‑00135‑833536635
    [Google Scholar]
  36. BrixN. SamagaD. BelkaC. ZitzelsbergerH. LauberK. Analysis of clonogenic growth in vitro.Nat. Protoc.202116114963499110.1038/s41596‑021‑00615‑034697469
    [Google Scholar]
  37. Grasl-KrauppB. Ruttkay-NedeckyB. KoudelkaH. BukowskaK. BurschW. Schulte-HermannR. In situ detection of fragmented DNA (TUNEL assay) fails to discriminate among apoptosis, necrosis, and autolytic cell death: A cautionary note.Hepatology1995215146514687737654
    [Google Scholar]
  38. SchneiderC.A. RasbandW.S. EliceiriK.W. NIH Image to ImageJ: 25 years of image analysis.Nat. Methods20129767167510.1038/nmeth.208922930834
    [Google Scholar]
  39. YangX. HuaC. LinL. GantingZ. Antimicrobial peptides as potential therapy for gastrointestinal cancers.Naunyn Schmiedebergs Arch. Pharmacol.2023396112831284110.1007/s00210‑023‑02536‑z37249612
    [Google Scholar]
  40. XuY. YaoY. WangL. ChenH. TanN. Hyaluronic acid coated liposomes co-delivery of natural cyclic peptide RA-XII and mitochondrial targeted photosensitizer for highly selective precise combined treatment of colon cancer.Int. J. Nanomedicine2021164929494210.2147/IJN.S31157734326635
    [Google Scholar]
  41. TorneselloA.L. BorrelliA. BuonaguroL. BuonaguroF.M. TorneselloM.L. Anti-microbial peptides as anti-cancer agents: Functional properties and biological activities.Molecules20202512285010.3390/molecules2512285032575664
    [Google Scholar]
  42. DengZ. GaoY. NguyenT. ChaiJ. WuJ. LiJ. Abdel-RahmanM.A. XuX. ChenX. The potent antitumor activity of Smp43 against non-small-cell lung cancer A549 cells via inducing membranolysis and mitochondrial dysfunction.Toxins (Basel)202315534710.3390/toxins1505034737235381
    [Google Scholar]
/content/journals/cpps/10.2174/0113892037363898250110053529
Loading
/content/journals/cpps/10.2174/0113892037363898250110053529
Loading

Data & Media loading...

Supplements

Supplementary material is available on the publisher’s website along with the published article.

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error
Please enter a valid_number test