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Insights into the anticancer properties of the first antimicrobial peptide from Archaea.

  • Author(s): Gaglione, Rosa
  • Pirone, Luciano
  • Farina, Biancamaria
  • Fusco, Salvatore
  • Smaldone, Giovanni
  • Aulitto, Martina
  • Dell'Olmo, Eliana
  • Roscetto, Emanuela
  • Del Gatto, Annarita
  • Fattorusso, Roberto
  • Notomista, Eugenio
  • Zaccaro, Laura
  • Arciello, Angela
  • Pedone, Emilia
  • Contursi, Patrizia
  • et al.
Abstract

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.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.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.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.VLL-28 represents the first ACP identified in an archaeal microorganism, exerting a trans-kingdom activity.

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