Cancer is a leading cause of death worldwide, characterized by uncontrolled cell growth and multiple mutations. Chemotherapy is often associated with harmful side effects, and cancer cells may become resistant through various mechanisms. Solutions to this issue include enhancing drug accumulation, inhibiting DNA repair, and activating apoptotic pathways. Antimicrobial peptides (AMPs), naturally occurring peptides belonging to the innate immune system, have a wide spectrum of cytotoxic activity against cancer cells and are a promising solution. They are composed of short chains of amino acids, characterized by high hydrophobicity, and a net charge mainly positive, and interact electrostatically with cancer cell membranes to disrupt their integrity, leading to cell death. Indeed, Cati…
Cancer is a leading cause of death worldwide, characterized by uncontrolled cell growth and multiple mutations. Chemotherapy is often associated with harmful side effects, and cancer cells may become resistant through various mechanisms. Solutions to this issue include enhancing drug accumulation, inhibiting DNA repair, and activating apoptotic pathways. Antimicrobial peptides (AMPs), naturally occurring peptides belonging to the innate immune system, have a wide spectrum of cytotoxic activity against cancer cells and are a promising solution. They are composed of short chains of amino acids, characterized by high hydrophobicity, and a net charge mainly positive, and interact electrostatically with cancer cell membranes to disrupt their integrity, leading to cell death. Indeed, Cationic Antimicrobial Peptides (CAPs), with positive net charge, selectively interact with the surface of cancer cells, sparing healthy cell with neutral charge, and disrupt their membranes through membranolytic actions (carpet model, barrel-stave model, aggregate channel model, and toroidal model). They also show non-membranolytic actions, including: inhibition of tumor angiogenesis, induction of tumor apoptosis, interference with functional proteins, induction of mitochondrial membrane disruption and subsequent release of cytochrome C, induction of cell cycle arrest, hemolytic activity. Insects, particularly the black soldier fly (BSF), Hermetia illucens L. (Diptera: Stratiomyidae), are among the richest and most innovative sources of AMPs, due to their ability to live in hostile environments. In this work the peptide fractions (PFs), rich in AMPs, extracted from the hemolymph of H. illucens larvae was tested on the HT29 and HCT116 human colorectal cancer cells, and on KATO III and AGS human gastric cancer cells. The PFs significantly inhibited tumor growth by inducing apoptosis, cell cycle arrest at the G2/M phase, and cytoskeleton reorganization leading to reduced motility. These effects, particularly evident in fractions obtained from Escherichia coli-infected larvae, also enhanced the efficacy of conventional chemotherapeutics, supporting the presence of biologically active molecules in the hemolymph of H. illucens and confirming insect-derived peptides as a promising research area in oncology.
Il cancro è una delle principali cause di morte in tutto il mondo, caratterizzata da una crescita incontrollata delle cellule e da molteplici mutazioni. La chemioterapia è spesso associata a effetti collaterali dannosi e le cellule tumorali possono diventare resistenti attraverso vari meccanismi. Le soluzioni a questa problematica comprendono l’aumento dell’accumulo di farmaci, l’inibizione della riparazione del DNA e l’attivazione di vie apoptotiche. I peptidi antimicrobici (Antimicrobial Peptides - AMPs), peptidi presenti in natura nel sistema immunitario innato, hanno un ampio spettro di attività citotossica contro le cellule tumorali e rappresentano una soluzione promettente. Si tratta di catene corte di aminoacidi, con un’elevata idrofobicità e una carica netta, per la maggior parte positiva, che interagiscono elettrostaticamente con le membrane delle cellule tumorali per interromperne l’integrità, portando alla morte cellulare. Infatti, i peptidi cationici antimicrobici (Cationic Antimicrobial Peptides - CAPs), a carica netta positiva, interagiscono con la superficie delle cellule tumorali, risparmiando le cellule normali a carica netta neutra, e di distruggere le loro membrane attraverso azioni membranolitiche (modello a tappeto, modello a botte, modello a canale aggregato e modello toroidale). Mostrano anche azioni non membranolitiche, tra cui: inibizione dell’angiogenesi tumorale, induzione dell’apoptosi tumorale, interferenza con proteine funzionali, induzione della rottura della membrana mitocondriale e conseguente rilascio di citocromo C, induzione dell’arresto del ciclo cellulare, attività emolitica. Gli insetti, in particolare la mosca soldato nera (BSF), Hermetia illucens L. (Diptera: Stratiomyidae), sono tra le fonti più ricche e innovative di AMP grazie alla loro capacità di vivere in ambienti ostili. In questo lavoro le frazioni peptidiche (PF), ricche di AMP, estratte dall’emolinfa delle larve dell’insetto H. illucens sono state testate su cellule umane di cancro del colon-retto HT29 e HCT116 e su cellule umane di cancro gastrico KATO III e AGS. Le PF hanno inibito significativamente la crescita tumorale inducendo l’apoptosi, arresto del ciclo cellulare nella fase G2/M e la riorganizzazione del citoscheletro con conseguente riduzione della motilità. Questi effetti, particolarmente evidenti nelle frazioni ottenute da larve infettate da Escherichia coli, hanno anche potenziato l’efficacia dei chemioterapici convenzionali, a sostegno della presenza di molecole III biologicamente attive nell’emolinfa di H. illucens e confermando i peptidi da insetto come una promettente area di ricerca in oncologia.
Identification and characterization of insect peptides with anticancer activity / Rinaldi, Roberta. - (2026 Jan 07).
Identification and characterization of insect peptides with anticancer activity
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2026-01-07
Abstract
Cancer is a leading cause of death worldwide, characterized by uncontrolled cell growth and multiple mutations. Chemotherapy is often associated with harmful side effects, and cancer cells may become resistant through various mechanisms. Solutions to this issue include enhancing drug accumulation, inhibiting DNA repair, and activating apoptotic pathways. Antimicrobial peptides (AMPs), naturally occurring peptides belonging to the innate immune system, have a wide spectrum of cytotoxic activity against cancer cells and are a promising solution. They are composed of short chains of amino acids, characterized by high hydrophobicity, and a net charge mainly positive, and interact electrostatically with cancer cell membranes to disrupt their integrity, leading to cell death. Indeed, Cationic Antimicrobial Peptides (CAPs), with positive net charge, selectively interact with the surface of cancer cells, sparing healthy cell with neutral charge, and disrupt their membranes through membranolytic actions (carpet model, barrel-stave model, aggregate channel model, and toroidal model). They also show non-membranolytic actions, including: inhibition of tumor angiogenesis, induction of tumor apoptosis, interference with functional proteins, induction of mitochondrial membrane disruption and subsequent release of cytochrome C, induction of cell cycle arrest, hemolytic activity. Insects, particularly the black soldier fly (BSF), Hermetia illucens L. (Diptera: Stratiomyidae), are among the richest and most innovative sources of AMPs, due to their ability to live in hostile environments. In this work the peptide fractions (PFs), rich in AMPs, extracted from the hemolymph of H. illucens larvae was tested on the HT29 and HCT116 human colorectal cancer cells, and on KATO III and AGS human gastric cancer cells. The PFs significantly inhibited tumor growth by inducing apoptosis, cell cycle arrest at the G2/M phase, and cytoskeleton reorganization leading to reduced motility. These effects, particularly evident in fractions obtained from Escherichia coli-infected larvae, also enhanced the efficacy of conventional chemotherapeutics, supporting the presence of biologically active molecules in the hemolymph of H. illucens and confirming insect-derived peptides as a promising research area in oncology.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11563/207676
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