The 6-amino-acid motif with reported antibacterial activity is shown in bold. Net charge was calculated by adding the net charges of basic/acidic residues at pH 7.0. m/z: for monoisotopic masses [M + H]+. * The m/z of the peptide was confirmed in its monomeric form prior to oxidative dimerization. MALDI–TOF: matrix-assisted laser desorption/ionization–time of flight.
The authors declare that they have no conflicts of interest.
Ethical approval
All animal experiments complied with the ARRIVE guidelines and the Guide for the Care and Use of Laboratory Animals. They were carried out following the EU directive 2010/63 for the protection of animals used for scientific purposes, and were approved by the Ethics Committee of the Sciences Faculty of the National University of Colombia (approved main project identification: RC# 678 of 2014).
Consent to participate
Not applicable.
Consent to publication
Not applicable.
Availability of data and materials
The raw data supporting the conclusions of this manuscript will be made available by the authors, without undue reservation, to any qualified researcher.
Funding
This study was developed as part of the Project: “Diseño, síntesis química y caracterización de péptidos derivados de lactoferricina y evaluación de su actividad anticancerígena. Fase II” approved by COLCIENCIAS, announcement 657-2014, contract: RC No. [678] of 2014. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
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References
Gatfield ER, Ince WHJ, Jefferies SJ. Squamous cell carcinoma of the oral cavity, oropharynx and upper oesophagus.Medicine. 2024;52:130–5. [DOI]
Pardo C, de Vries E. Oral and oropharyngeal cancer in Colombia: an experience in a middle-income country cancer institute (2004–2013).Oral Cancer. 2018;2:19–26. [DOI]
Silvestre-Donat FJ, Puente Sandoval A. Efectos adversos del tratamiento del cáncer oral.Av Odontoestomatol. 2008;24:111–21. [DOI]
Yuan J, Shi K, Chen G, Xu W, Qiu L, Fei Y, et al. A Network Meta-Analysis of the Systemic Therapies in Unresectable Head and Neck Squamous Cell Carcinoma.Cancer Control. 2024;31:10732748241255535. [DOI] [PubMed] [PMC]
Chiari F, Filippini DM, Fermi M, Presutti L, Caporale CD, Bertino G, et al. Survival behavior of patients treated with curative and palliative electrochemotherapy for oral and oropharyngeal cancer: a systematic review.Eur Arch Otorhinolaryngol. 2026;283:2665–80. [DOI] [PubMed]
Chu HL, Yip BS, Chen KH, Yu HY, Chih YH, Cheng HT, et al. Novel antimicrobial peptides with high anticancer activity and selectivity.PLoS One. 2015;10:e0126390. [DOI] [PubMed] [PMC]
da Costa JP, Carvalhais V, Amado F, Silva A, Nogueira-Ferreira R, Ferreira R, et al. Anti-tumoral activity of human salivary peptides.Peptides. 2015;71:170–8. [DOI] [PubMed]
Liu X, Li Y, Li Z, Lan X, Leung P, Li J, et al. Mechanism of Anticancer Effects of Antimicrobial Peptides.J Fiber Bioeng Inform. 2015;8:25–36. [DOI]
Xiao YF, Jie MM, Li BS, Hu CJ, Xie R, Tang B, et al. Peptide-Based Treatment: A Promising Cancer Therapy.J Immunol Res. 2014;2015:1–13. [DOI]
Wu D, Gao Y, Qi Y, Chen L, Ma Y, Li Y. Peptide-based cancer therapy: opportunity and challenge.Cancer Lett. 2014;351:13–22. [DOI] [PubMed]
Morillo I, Zulaica J, R Caballero A, Auzmendi-Iriarte J, Largo E, Apellaniz B, et al. Engineering a single-chain immunoglobulin scaffold loaded with a latent-releasable cytotoxic pore-forming peptide.Commun Biol. 2025;8:1665. [DOI] [PubMed] [PMC]
Li C, Li S, Lv L, Chen Y, Yang S, Lu Y, et al. Mitochondria-Targeting Antimicrobial Peptide (AMP) Regulating N6-Methyladenosine (m6A) Modification to Promote Colon Cancer Ferroptosis.Bioconjug Chem. 2025;36:2497–506. [DOI] [PubMed] [PMC]
Kapan E, Uslu C, Arab H, Ahmed L, Ali R, Tereshchenkov AG, et al. Toward Mitochondrial Targeting of Resistant Triple-Negative Breast Cancer Using Triphenylphosphonium-Conjugated Antimicrobial Peptides.ACS Pharmacol Transl Sci. 2025;8:4159–71. [DOI] [PubMed] [PMC]
Włodarczyk J, Kamysz E, Fichna J. Synthesis and evaluation of KR-12, an LL-37 fragment, and its short-chain fatty acid derivatives: selective cytotoxicity in colorectal cancer cells and anti-tumor efficacy in an azoxymethane/DSS-induced colitis-associated cancer mouse model.Pharmacol Rep. 2025;77:1689–702. [DOI] [PubMed] [PMC]
Hao Y, Yang N, Teng D, Wang X, Mao R, Wang J. A review of the design and modification of lactoferricins and their derivatives.Biometals. 2018;31:331–41. [DOI] [PubMed]
Vogel HJ, Schibli DJ, Jing W, Lohmeier-Vogel EM, Epand RF, Epand RM. Towards a structure-function analysis of bovine lactoferricin and related tryptophan- and arginine-containing peptides.Biochem Cell Biol. 2002;80:49–63. [DOI] [PubMed]
Schibli DJ, Hwang PM, Vogel HJ. The structure of the antimicrobial active center of lactoferricin B bound to sodium dodecyl sulfate micelles.FEBS Lett. 1999;446:213–7. [DOI] [PubMed]
Nguyen LT, Schibli DJ, Vogel HJ. Structural studies and model membrane interactions of two peptides derived from bovine lactoferricin.J Pept Sci. 2005;11:379–89. [DOI] [PubMed]
Zhang Y, Lima CF, Rodrigues LR. Anticancer effects of lactoferrin: underlying mechanisms and future trends in cancer therapy.Nutr Rev. 2014;72:763–73. [DOI] [PubMed]
Yin CM, Wong JH, Xia J, Ng TB. Studies on anticancer activities of lactoferrin and lactoferricin.Curr Protein Pept Sci. 2013;14:492–503. [DOI] [PubMed]
Riedl S, Leber R, Rinner B, Schaider H, Lohner K, Zweytick D. Human lactoferricin derived di-peptides deploying loop structures induce apoptosis specifically in cancer cells through targeting membranous phosphatidylserine.Biochim Biophys Acta. 2015;1848:2918–31. [DOI] [PubMed]
Wang S, Tu J, Zhou C, Li J, Huang L, Tao L, et al. The effect of Lfcin-B on non-small cell lung cancer H460 cells is mediated by inhibiting VEGF expression and inducing apoptosis.Arch Pharm Res. 2015;38:261–71. [DOI] [PubMed]
Sheng M, Zhao Y, Zhang A, Wang L, Zhang G. The effect of LfcinB9 on human ovarian cancer cell SK-OV-3 is mediated by inducing apoptosis.J Pept Sci. 2014;20:803–10. [DOI] [PubMed]
Fang B, Zhang M, Tian M, Jiang L, Guo HY, Ren FZ. Bovine lactoferrin binds oleic acid to form an anti-tumor complex similar to HAMLET.Biochim Biophys Acta. 2014;1841:535–43. [DOI] [PubMed]
Hilchie AL, Vale R, Zemlak TS, Hoskin DW. Generation of a hematologic malignancy-selective membranolytic peptide from the antimicrobial core (RRWQWR) of bovine lactoferricin.Exp Mol Pathol. 2013;95:192–8. [DOI] [PubMed]
Eliassen LT, Haug BE, Berge G, Rekdal O. Enhanced antitumour activity of 15-residue bovine lactoferricin derivatives containing bulky aromatic amino acids and lipophilic N-terminal modifications.J Pept Sci. 2003;9:510–7. [DOI] [PubMed]
Mader JS, Richardson A, Salsman J, Top D, de Antueno R, Duncan R, et al. Bovine lactoferricin causes apoptosis in Jurkat T-leukemia cells by sequential permeabilization of the cell membrane and targeting of mitochondria.Exp Cell Res. 2007;313:2634–50. [DOI] [PubMed]
Castellar-Almonacid DA, Barragán-Cárdenas AC, Rodríguez-Mejia KG, Maldonado-Sanabria LA, Ardila-Chantré N, Mendoza-Mendoza JD, et al. Non-steroidal anti-inflammatory drugs conjugated to a synthetic peptide exhibit in vitro cytotoxic activity against cervical cancer and melanoma cells.RSC Med Chem. 2025;16:4170–82. [DOI] [PubMed] [PMC]
León-Calvijo MA, Leal-Castro AL, Almanzar-Reina GA, Rosas-Pérez JE, García-Castañeda JE, Rivera-Monroy ZJ. Antibacterial activity of synthetic peptides derived from lactoferricin against Escherichia coli ATCC 25922 and Enterococcus faecalis ATCC 29212.Biomed Res Int. 2015;2015:453826. [DOI] [PubMed] [PMC]
Huertas Méndez NJ, Vargas Casanova Y, Gómez Chimbi AK, Hernández E, Leal Castro AL, Melo Diaz JM, et al. Synthetic Peptides Derived from Bovine Lactoferricin Exhibit Antimicrobial Activity against E. coli ATCC 11775, S. maltophilia ATCC 13636 and S. enteritidis ATCC 13076.Molecules. 2017;22:452. [DOI] [PubMed] [PMC]
Vargas Casanova Y, Rodríguez Guerra JA, Umaña Pérez YA, Leal Castro AL, Almanzar Reina G, García Castañeda JE, et al. Antibacterial Synthetic Peptides Derived from Bovine Lactoferricin Exhibit Cytotoxic Effect against MDA-MB-468 and MDA-MB-231 Breast Cancer Cell Lines.Molecules. 2017;22:1641. [DOI] [PubMed] [PMC]
Solarte VA, Conget P, Vernot JP, Rosas JE, Rivera ZJ, García JE, et al. A tetrameric peptide derived from bovine lactoferricin as a potential therapeutic tool for oral squamous cell carcinoma: A preclinical model.PLoS One. 2017;12:e0174707. [DOI] [PubMed] [PMC]
Vega Chaparro SC, Valencia Salguero JT, Martínez Baquero DA, Rosas Pérez JE. Effect of Polyvalence on the Antibacterial Activity of a Synthetic Peptide Derived from Bovine Lactoferricin against Healthcare-Associated Infectious Pathogens.Biomed Res Int. 2018;2018:5252891. [DOI] [PubMed] [PMC]
Martínez B DA, Barato Gómez PA, Iregui Castro CA, Rosas Pérez JE. DMBA-Induced Oral Carcinoma in Syrian Hamster: Increased Carcinogenic Effect by Dexamethasone Coexposition.Biomed Res Int. 2020;2020:1470868. [DOI] [PubMed] [PMC]
Vergel Galeano CF, Rivera Monroy ZJ, Rosas Pérez JE, García Castañeda JE. Efficient Synthesis of Peptides with 4-Methylpiperidine as Fmoc Removal Reagent by Solid Phase Synthesis.J Mex Chem Soc. 2014;58:386–92. [DOI]
Faustino-Rocha A, Oliveira PA, Pinho-Oliveira J, Teixeira-Guedes C, Soares-Maia R, da Costa RG, et al. Estimation of rat mammary tumor volume using caliper and ultrasonography measurements.Lab Anim (NY). 2013;42:217–24. [DOI] [PubMed]
Mader JS, Salsman J, Conrad DM, Hoskin DW. Bovine lactoferricin selectively induces apoptosis in human leukemia and carcinoma cell lines.Mol Cancer Ther. 2005;4:612–24. [DOI] [PubMed]
Eloïse L, Petit L, Nominé Y, Heurtault B, Ben Hadj Kaddour I, Senger B, et al. The antibacterial properties of branched peptides based on poly(l-arginine): In vitro antibacterial evaluation and molecular dynamic simulations.Eur J Med Chem. 2024;268:116224. [DOI] [PubMed]
Solarte VA, Rosas JE, Rivera ZJ, Arango-Rodríguez ML, García JE, Vernot JP. A Tetrameric Peptide Derived from Bovine Lactoferricin Exhibits Specific Cytotoxic Effects against Oral Squamous-Cell Carcinoma Cell Lines.Biomed Res Int. 2015;2015:630179. [DOI] [PubMed] [PMC]
Vega SC, Martínez DA, Chalá MDS, Vargas HA, Rosas JE. Design, Synthesis and Evaluation of Branched RRWQWR-Based Peptides as Antibacterial Agents Against Clinically Relevant Gram-Positive and Gram-Negative Pathogens.Front Microbiol. 2018;9:329. [DOI] [PubMed] [PMC]
Cárdenas-Martínez KJ, Reyes-Calderon JE, Parra-Giraldo CM, Vargas-Casanova Y, Barragán-Cárdenas AC, Fierro-Medina R, et al. Behind anticancer molecules: lactoferricin dimeric peptides with fast, selective, persistent and broad-spectrum cytotoxic effect.Explor Drug Sci. 2025;3:100891. [DOI]
Huni KC, Cheung J, Sullivan M, Robison WT, Howard KM, Kingsley K. Chemotherapeutic Drug Resistance Associated with Differential miRNA Expression of miR-375 and miR-27 among Oral Cancer Cell Lines.Int J Mol Sci. 2023;24:1244. [DOI] [PubMed] [PMC]
Strøm MB, Haug BE, Rekdal O, Skar ML, Stensen W, Svendsen JS. Important structural features of 15-residue lactoferricin derivatives and methods for improvement of antimicrobial activity.Biochem Cell Biol. 2002;80:65–74. [DOI] [PubMed]
Richardson A, de Antueno R, Duncan R, Hoskin DW. Intracellular delivery of bovine lactoferricin's antimicrobial core (RRWQWR) kills T-leukemia cells.Biochem Biophys Res Commun. 2009;388:736–41. [DOI] [PubMed]
Lu Y, Zhang TF, Shi Y, Zhou HW, Chen Q, Wei BY, et al. PFR peptide, one of the antimicrobial peptides identified from the derivatives of lactoferrin, induces necrosis in leukemia cells.Sci Rep. 2016;6:20823. [DOI] [PubMed] [PMC]
Taghizadeh MS, Niazi A, Moghadam A, Afsharifar AR. Novel bioactive peptides of Achillea eriophora show anticancer and antioxidant activities.Bioorg Chem. 2021;110:104777. [DOI] [PubMed]
Chen YK, Lin LM. DMBA-induced hamster buccal pouch carcinoma and VX2-induced rabbit cancer as a model for human oral carcinogenesis.Expert Rev Anticancer Ther. 2010;10:1485–96. [DOI] [PubMed]
Stadler ME, Patel MR, Couch ME, Hayes DN. Molecular biology of head and neck cancer: risks and pathways.Hematol Oncol Clin North Am. 2008;22:1099–124. [DOI] [PubMed] [PMC]
Szczepanski C, Tenstad O, Baumann A, Martinez A, Myklebust R, Bjerkvig R, et al. Identification of a novel lytic peptide for the treatment of solid tumours.Genes Cancer. 2014;5:186–200. [DOI] [PubMed] [PMC]
Kamarajan P, Hayami T, Matte B, Liu Y, Danciu T, Ramamoorthy A, et al. Nisin ZP, a Bacteriocin and Food Preservative, Inhibits Head and Neck Cancer Tumorigenesis and Prolongs Survival.PLoS One. 2015;10:e0131008. [DOI] [PubMed] [PMC]
