Rosa Gaglione1, Luciano Pirone2, Biancamaria Farina3, Salvatore Fusco4, Giovanni Smaldone5, Martina Aulitto6, Eliana Dell'Olmo1, Emanuela Roscetto7, Annarita Del Gatto8, Roberto Fattorusso9, Eugenio Notomista6, Laura Zaccaro8, Angela Arciello10, Emilia Pedone11, Patrizia Contursi12. 1. Department of Chemical Sciences, University of Naples Federico II, 80126 Naples, Italy. 2. Institute of Biostructures and Bioimaging, Italian Research National Council, Naples, Italy. 3. Institute of Biostructures and Bioimaging, Italian Research National Council, Naples, Italy; Advanced Accelerator Applications, 81100 Caserta, Italy. 4. Department of Biology, University of Naples Federico II, Complesso Universitario Monte S. Angelo, Via Cinthia, 80126 Naples, Italy.; Division of Industrial Biotechnology, Department of Biology and Biological Engineering, Chalmers University of Technology, Göteborg, Sweden. 5. IRCCS SDN, Via E. Gianturco 113, 80143 Naples, Italy. 6. Department of Biology, University of Naples Federico II, Complesso Universitario Monte S. Angelo, Via Cinthia, 80126 Naples, Italy. 7. Department of Molecular Medicine and Medical Biotechnology, Federico II University Medical School, Italy. 8. Institute of Biostructures and Bioimaging, Italian Research National Council, Naples, Italy; Research Centre on Bioactive Peptides (CIRPeB), University of Naples "Federico II", Via Mezzocannone 16, 80134 Naples, Italy. 9. Research Centre on Bioactive Peptides (CIRPeB), University of Naples "Federico II", Via Mezzocannone 16, 80134 Naples, Italy; Department of Environmental, Biological and Pharmaceutical Sciences and Technologies, University of Campania-Luigi Vanvitelli, 81100 Caserta, Italy. 10. Department of Chemical Sciences, University of Naples Federico II, 80126 Naples, Italy; National Institute of Biostructures and Biosystems (INBB), Italy. Electronic address: anarciel@unina.it. 11. Institute of Biostructures and Bioimaging, Italian Research National Council, Naples, Italy; Research Centre on Bioactive Peptides (CIRPeB), University of Naples "Federico II", Via Mezzocannone 16, 80134 Naples, Italy. Electronic address: empedone@unina.it. 12. Department of Biology, University of Naples Federico II, Complesso Universitario Monte S. Angelo, Via Cinthia, 80126 Naples, Italy.. Electronic address: contursi@unina.it.
Abstract
BACKGROUND: The peptide VLL-28, identified in the sequence of an archaeal protein, the transcription factor Stf76 from Sulfolobus islandicus, was previously identified and characterized as an antimicrobial peptide, possessing a broad-spectrum antibacterial activity. METHODS: Through a combined approach of NMR and Circular Dichroism spectroscopy, Dynamic Light Scattering, confocal microscopy and cell viability assays, the interaction of VLL-28 with the membranes of both parental and malignant cell lines has been characterized and peptide mechanism of action has been studied. RESULTS: It is here demonstrated that VLL-28 selectively exerts cytotoxic activity against murine and human tumor cells. By means of structural methodologies, VLL-28 interaction with the membranes has been proven and the binding residues have been identified. Confocal microscopy data show that VLL-28 is internalized only into tumor cells. Finally, it is shown that cell death is mainly caused by a time-dependent activation of apoptotic pathways. CONCLUSIONS: VLL-28, deriving from the archaeal kingdom, is here found to be endowed with selective cytotoxic activity towards both murine and human cancer cells and consequently can be classified as an ACP. GENERAL SIGNIFICANCE: VLL-28 represents the first ACP identified in an archaeal microorganism, exerting a trans-kingdom activity.
BACKGROUND: The peptide VLL-28, identified in the sequence of an archaeal protein, the transcription factor Stf76 from Sulfolobus islandicus, was previously identified and characterized as an antimicrobial peptide, possessing a broad-spectrum antibacterial activity. METHODS: Through a combined approach of NMR and Circular Dichroism spectroscopy, Dynamic Light Scattering, confocal microscopy and cell viability assays, the interaction of VLL-28 with the membranes of both parental and malignant cell lines has been characterized and peptide mechanism of action has been studied. RESULTS: It is here demonstrated that VLL-28 selectively exerts cytotoxic activity against murine and humantumor cells. By means of structural methodologies, VLL-28 interaction with the membranes has been proven and the binding residues have been identified. Confocal microscopy data show that VLL-28 is internalized only into tumor cells. Finally, it is shown that cell death is mainly caused by a time-dependent activation of apoptotic pathways. CONCLUSIONS: VLL-28, deriving from the archaeal kingdom, is here found to be endowed with selective cytotoxic activity towards both murine and humancancer cells and consequently can be classified as an ACP. GENERAL SIGNIFICANCE: VLL-28 represents the first ACP identified in an archaeal microorganism, exerting a trans-kingdom activity.
Authors: Martina Aulitto; Salvatore Fusco; David Benjamin Nickel; Simonetta Bartolucci; Patrizia Contursi; Carl Johan Franzén Journal: Biotechnol Biofuels Date: 2019-02-28 Impact factor: 6.040
Authors: Emanuela Roscetto; Marco Masi; Matilde Esposito; Roberta Di Lecce; Antonella Delicato; Lucia Maddau; Viola Calabrò; Antonio Evidente; Maria Rosaria Catania Journal: Toxins (Basel) Date: 2020-07-08 Impact factor: 4.546
Authors: Rosa Gaglione; Giovanni Smaldone; Angela Cesaro; Mariano Rumolo; Maria De Luca; Rocco Di Girolamo; Luigi Petraccone; Pompea Del Vecchio; Rosario Oliva; Eugenio Notomista; Emilia Pedone; Angela Arciello Journal: Pharmaceuticals (Basel) Date: 2021-06-29