Skip to content
2000
  1. Home
  2. A-Z Publications
  3. Recent Patents on Biotechnology
  4. Volume 19, Issue 2
  5. Article
  • ISSN: 1872-2083
  • E-ISSN: 2212-4012

Abstract

Background

Peptide-based therapy has emerged as a promising avenue for treating various disorders, and recent research has highlighted the potential of anti-cancer peptides (ACPs) in cancer treatment. In this context, this study aimed to design a novel peptide incorporating a tumor-homing peptide (RGD) and C-amidation to enhance its anticancer activity, particularly against liver (HepG2) and colon (HCT-116) cancer cell lines.

Objectives

The primary objective was to design a peptide with improved anticancer properties by leveraging the tumor-homing capabilities of RGD and enhancing its activity through C-amidation. The study sought to evaluate the cytotoxicity of the designed peptide against red blood cells (RBCs) and normal Vero cells. Furthermore, the anticancer efficacy of the peptide was assessed in hepatocellular carcinoma (HepG2) and colon cancer (HCT-116) cell lines. The specific objectives included examining the apoptotic induction and morphological changes in treated cells compared to untreated cells.

Methods

The peptide was designed using the ACPred-FL bioinformatics tool, and its cytotoxicity was assessed through hemolysis assays against RBCs and normal Vero cells. Anticancer activity was evaluated against HepG2 and HCT-116 cell lines. The analysis of apoptotic induction involved measuring the relative gene expression of oncogenic marker BCL2 and apoptotic markers (BAX, BID, CAS-8). Additionally, Cytopathological examination and Western Blot analysis were employed to study morphological changes and confirm the quantification of relevant markers.

Results

The designed peptide, consisting of twelve amino acids with a molecular mass of 1230.6233 Da and an isoelectric point of 9.81, exhibited low erythrocyte lysis and minimal toxicity to normal cells. The IC values demonstrated significant anticancer activity against both HepG2 (36.49±2.6 µg/mL) and HCT-116 (11.03±2.5 µg/mL) cell lines. Treated cells exhibited a significant decrease in the oncogenic marker BCL2 and an upregulation of apoptotic markers (BAX, BID, CAS-8). Western Blot analysis confirmed these results in addition to cytopathological examination that scattered apoptotic and degenerative changes.

Conclusion

The designed peptide is considered a patent product that displayed remarkable anticancer activity against hepatocellular carcinoma and colon cancer cell lines, effectively modulating apoptotic and oncogenic markers. These findings highlight the potential of the peptide as a therapeutic agent for cancer treatment, emphasizing its clinical significance in combating liver and colon cancers. Nonetheless, further research and development are warranted to explore the translational potential of this peptide in clinical studies.

© 2025 Bentham Science Publishers
Loading

Article metrics loading...

/content/journals/biot/10.2174/0118722083300452240315035722
2024-03-20
2025-04-23

  • From This Site

    /content/journals/biot/10.2174/0118722083300452240315035722
    dcterms_title,dcterms_subject,pub_keyword
    -contentType:Contributor -contentType:Concept -contentType:Institution
    10
    5
Loading full text...

Full text loading...

References

  1. KinsellaN. Registration of peptides and proteins. Pharmaceutical Formulation Development of Peptides and Proteins.2nd edUnited KingdomTaylor & Francis201233936610.1201/b12951
     [Google Scholar]
  2. GrigolavaM. VishnepolskyB. PirtskhalavaM. Antimicrobial peptides as anticancer agents.Biopolymers Cell20153156
     [Google Scholar]
  3. DissanayakeS. DennyW.A. GamageS. SarojiniV. Recent developments in anticancer drug delivery using cell penetrating and tumor targeting peptides.J. Control. Release2017250627610.1016/j.jconrel.2017.02.00628167286
     [Google Scholar]
  4. ScodellerP. AsciuttoE.K. Targeting tumors using peptides.Molecules202025480810.3390/molecules2504080832069856
     [Google Scholar]
  5. ThomaB. PownerM.W. Selective synthesis of lysine peptides and the prebiotically plausible synthesis of catalytically active diaminopropionic acid peptide nitriles in water.J. Am. Chem. Soc.202314553121313010.1021/jacs.2c1249736700882
     [Google Scholar]
  6. HayashiM.A.F. DucancelF. KonnoK. Natural peptides with potential applications in drug development, diagnosis, and/or biotechnology.Int. J. Pept.201220121210.1155/2012/75783822927866
     [Google Scholar]
  7. XiaoY.F. JieM.M. LiB.S. Peptide-based treatment: A promising cancer therapy.J. Immunol. Res.2015201511310.1155/2015/76182026568964
     [Google Scholar]
  8. DanhierF. Le BretonA. PréatV. RGD-based strategies to target alpha(v) beta(3) integrin in cancer therapy and diagnosis.Mol. Pharm.20129112961297310.1021/mp300273322967287
     [Google Scholar]
  9. MuraM. WangJ. ZhouY. The effect of amidation on the behaviour of antimicrobial peptides.Eur. Biophys. J.201645319520710.1007/s00249‑015‑1094‑x26745958
     [Google Scholar]
  10. HeimbachJ.K. KulikL.M. FinnR.S. AASLD guidelines for the treatment of hepatocellular carcinoma.Hepatology201867135838010.1002/hep.2908628130846
     [Google Scholar]
  11. RashdanH.R.M. OkashaH. SalemM.M. Abd El-HadyB.M. EkramB. Investigation of novel HCV therapies: Boscia angustifalia & Boscia senegalensis extracts loaded on galactosylated chitosan nanoparticles synthesized by eco-friendly method for HCV treatment.Int. J. Biol. Macromol.202324512542010.1016/j.ijbiomac.2023.12542037353115
     [Google Scholar]
  12. MetwallyIH ShetiwyM ElalfyAF AbouzidA SalehSS HamdyM Epidemiology and survival of colon cancer among Egyptians: A retrospective study.J Coloproctol (Rio J)2018381024910.1016/j.jcol.2017.09.418
     [Google Scholar]
  13. DekkerE. TanisP.J. VleugelsJ.L.A. KasiP.M. WallaceM.B. Colorectal cancer.Lancet2019394102071467148010.1016/S0140‑6736(19)32319‑031631858
     [Google Scholar]
  14. BuschauerS. KochA. WiggermannP. MüllerM. HellerbrandC. Hepatocellular carcinoma cells surviving doxorubicin treatment exhibit increased migratory potential and resistance to doxorubicin re-treatment in vitro.Oncol. Lett.20181544635464010.3892/ol.2018.788729541235
     [Google Scholar]
  15. OkashaH. AboushoushaT. CoimbraM.A. CardosoS.M. GhareebM.A. Metabolite profiling of Alocasia gigantea leaf extract and its potential anticancer effect through autophagy in hepatocellular carcinoma.Molecules20222723850410.3390/molecules2723850436500595
     [Google Scholar]
  16. OkashaH. Fundamental uses of peptides as a new model in both treatment and diagnosis.Recent Pat. Biotechnol.2023711810.2174/187220831766623051214350838282442
     [Google Scholar]
  17. WangL. DongC. LiX. HanW. SuX. Anticancer potential of bioactive peptides from animal sources.Oncol. Rep.201738263765110.3892/or.2017.577828677775
     [Google Scholar]
  18. WeiL. ZhouC. ChenH. SongJ. SuR. ACPred-FL: A sequence-based predictor using effective feature representation to improve the prediction of anti-cancer peptides.Bioinformatics201834234007401610.1093/bioinformatics/bty45129868903
     [Google Scholar]
  19. MorsiE.A. AhmedH.O. Abdel-HadyH. El-SayedM. ShemisM.A. GC-analysis, and antioxidant, anti-inflammatory, and anticancer activities of some extracts and fractions of Linum usitatissimum.Curr. Bioact. Compd.20201691306131810.2174/1573407216666200206095954
     [Google Scholar]
  20. GrecoI. MolchanovaN. HolmedalE. Correlation between hemolytic activity, cytotoxicity and systemic in vivo toxicity of synthetic antimicrobial peptides.Sci. Rep.20201011320610.1038/s41598‑020‑69995‑932764602
     [Google Scholar]
  21. HendO. MarwaH. TarekA. SafiaS. Effect of Interferon-Beta (IFN-β) on tumor suppressor and apoptotic markers in hepatocellular carcinoma cell line.Int J Res Pharm Sci20191042936294310.26452/ijrps.v10i4.1574
     [Google Scholar]
  22. SaberM.A. OkashaH. KhorshedF. SamirS. A novel cell-based in vitro assay for antiviral activity of Interferons α, β, and γ by qPCR of MxA gene expression.Recent Pat. Biotechnol.2021151677510.2174/187220831466620111210505333183215
     [Google Scholar]
  23. GolestaniE.B. SanatiM.H. HoushmandM. AtaeiM. AkbarianF. ShakhssalimN. Expression and prognostic significance of bcl-2 and bax in the progression and clinical outcome of transitional bladder cell carcinoma.Cell J.201415435636324381861
     [Google Scholar]
  24. KhoshsiratS. AbbaszadehH.A. KhoramgahM.S. Protective effect of photobiomodulation therapy and bone marrow stromal stem cells conditioned media on pheochromocytoma cell line 12 against oxidative stress induced by hydrogen peroxide.J. Lasers Med. Sci.201910316317010.15171/jlms.2019.2631749940
     [Google Scholar]
  25. YuanY.G. ZhangS. HwangJ.Y. KongI.K. Silver nanoparticles potentiates cytotoxicity and apoptotic potential of camptothecin in human cervical cancer cells.Oxid. Med. Cell. Longev.2018201812110.1155/2018/612132830647812
     [Google Scholar]
  26. BorhaniN. ManoochehriM. SalehG.S. Ghaffari NovinM. MansouriA. OmraniM.D. Decreased expression of proapoptotic genes caspase-8- and BCL2-associated agonist of cell death (BAD) in ovarian cancer.Clin Ovarian Gynecol Cancer201471-2182310.1016/j.cogc.2014.12.004
     [Google Scholar]
  27. SongC. HanY. LuoH. HOXA10 induces BCL2 expression, inhibits apoptosis, and promotes cell proliferation in gastric cancer.Cancer Med.20198125651566110.1002/cam4.244031364281
     [Google Scholar]
  28. NasrS.M. SamirS. OkashaH. Interdisciplinary gene manipulation, molecular cloning, and recombinant expression of modified human growth hormone isoform-1 in E. coli system.Int. J. Biol. Macromol.2024257Pt 112863710.1016/j.ijbiomac.2023.12863738061513
     [Google Scholar]
  29. KoomenB.M. van der Starre-GaalJ. VonkJ.M. Formalin fixation for optimal concordance of programmed death‐ligand 1 immunostaining between cytologic and histologic specimens from patients with non-small cell lung cancer.Cancer Cytopathol.2021129430431710.1002/cncy.2238333108706
     [Google Scholar]
  30. ChiangjongW. ChutipongtanateS. HongengS. Anticancer peptide: Physicochemical property, functional aspect and trend in clinical application (Review).Int. J. Oncol.202057367869610.3892/ijo.2020.509932705178
     [Google Scholar]
  31. RoudiR. SynN.L. RoudbaryM. Antimicrobial peptides as biologic and immunotherapeutic agents against cancer: A comprehensive overview.Front. Immunol.20178132010.3389/fimmu.2017.0132029081781
     [Google Scholar]
  32. RuoslahtiE. Tumor penetrating peptides for improved drug delivery.Adv. Drug Deliv. Rev.2017110-11131210.1016/j.addr.2016.03.00827040947
     [Google Scholar]
  33. TeesaluT. SugaharaK.N. RuoslahtiE. Tumor-penetrating peptides.Front. Oncol.2013321610.3389/fonc.2013.0021623986882
     [Google Scholar]
  34. KumarD. EipperB.A. MainsR.E. Amidation. Reference Module in Biomedical Sciences.Elsevier: Amsterdam, The Netherlands20141510.1016/B978‑0‑12‑801238‑3.04040‑X
     [Google Scholar]
  35. XieM. LiuD. YangY. Anti-cancer peptides: Classification, mechanism of action, reconstruction and modification.Open Biol.202010720000410.1098/rsob.20000432692959
     [Google Scholar]
  36. KouchakzadehH. SafaviM.S. ShojaosadatiS.A. Protein and peptide nanoparticles for drug delivery.1st edAmsterdam, The NetherlandsElsevier20159810.1016/bs.apcsb.2014.11.002
     [Google Scholar]
  37. PandeyS. MalviyaG. ChottovaD.M. Role of peptides in diagnostics.Int. J. Mol. Sci.20212216882810.3390/ijms2216882834445532
     [Google Scholar]
  38. CapassoD. Del GattoA. ComegnaD. Selective targeting of αvβ5 integrin in HepG2 cell line by RGDechi15D peptide.Molecules20202518429810.3390/molecules2518429832961684
     [Google Scholar]
  39. HolohanC. Van SchaeybroeckS. LongleyD.B. JohnstonP.G. Cancer drug resistance: An evolving paradigm.Nat. Rev. Cancer2013131071472610.1038/nrc359924060863
     [Google Scholar]
  40. ChristianA. Rgd-containing peptide and use thereof for cancer treatment. WO2021185719A1. WIPO.PCT2021
     [Google Scholar]
/content/journals/biot/10.2174/0118722083300452240315035722
Loading
Development of a Novel Peptide with RGD Tumor Homing Motif: Evaluation of its Anticancer Potential in Hepatocellular Carcinoma and Colon Cancer Cells
Recent Pat. Biotechnol. 19, 128 (2025); https://doi.org/10.2174/0118722083300452240315035722
/content/journals/biot/10.2174/0118722083300452240315035722
/content/journals/biot/10.2174/0118722083300452240315035722
Loading

Data & Media loading...


  • Article Type:     Research Article
Keyword(s): ACPs; apoptosis; colon cancer; hepatocellular carcinoma; Peptide; tumor homing peptide

Most Cited Most Cited RSS feed

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