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

Rosa Gaglione, Luciano Pirone, Biancamaria Farina, Salvatore Fusco, Giovanni Smaldone, Martina Aulitto, Eliana Dell'Olmo, Emanuela Roscetto, Annarita Del Gatto, Roberto Fattorusso, Eugenio Notomista, Laura Zaccaro, Angela Arciello, Emilia Pedone, Patrizia Contursi

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)2155-2164
Number of pages10
JournalBiochimica et Biophysica Acta - General Subjects
Volume1861
Issue number9
DOIs
Publication statusPublished - Sep 1 2017

Keywords

  • Anticancer peptide
  • Antimicrobial peptide
  • Archaea
  • Peptide-membrane interactions
  • Sulfolobus

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology

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