Insights into the anticancer properties of the first antimicrobial peptide from Archaea
Journal article, 2017
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.
Archaea
Antimicrobial peptide
Sulfolobus
Peptide-membrane interactions
Anticancer peptide
Author
R. Gaglione
Universita degli Studi di Napoli Federico II
L. Pirone
Consiglio Nazionale delle Ricerche
B. Farina
Consiglio Nazionale delle Ricerche
Advanced Accelerator Applications
Salvatore Fusco
Chalmers, Biology and Biological Engineering, Industrial Biotechnology
G. Smaldone
IRCCS Fondazione SDN
Martina Aulitto
Universita degli Studi di Napoli Federico II
E. Dell'Olmo
Universita degli Studi di Napoli Federico II
E. Roscetto
Med. School University Federico II
A. Del Gatto
Consiglio Nazionale delle Ricerche
Universita degli Studi di Napoli Federico II
R. Fattorusso
University of Campania Luigi Vanvitelli
Universita degli Studi di Napoli Federico II
E. Notomista
Universita degli Studi di Napoli Federico II
L. Zaccaro
Universita degli Studi di Napoli Federico II
Consiglio Nazionale delle Ricerche
A. Arciello
Istituto Nazionale di Biostrutture e Biosistemi
Universita degli Studi di Napoli Federico II
Emilia Pedone
Consiglio Nazionale delle Ricerche
Universita degli Studi di Napoli Federico II
Patrizia Contursi
Universita degli Studi di Napoli Federico II
Biochimica et Biophysica Acta - General Subjects
0304-4165 (ISSN)
Vol. 1861 9 2155-2164Subject Categories (SSIF 2011)
Biochemistry and Molecular Biology
DOI
10.1016/j.bbagen.2017.06.009