Antibiotic magainins exert cytolytic activity against transformed cell lines through channel formation.
Magainins are an ionophoric class of vertebrate peptides with antibiotic activity against various microorganisms. Here we show that magainin 2 and synthetic analogues can rapidly and irreversibly lyse hematopoietic tumor and solid tumor target cells with a relative cytotoxic potency that parallels their antibacterial efficacy and at concentrations that are relatively nontoxic to well-differentiated cells. The cytotoxicity is prevented by cell depolarization. Magainins represent a natural cytolytic agent in vertebrates and may provide another therapeutic strategy for certain tumors.
Cruciani
R A
RA
Laboratory of Neurophysiology, National Institute of Neurological and Communicative Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892.
Barker
J L
JL
Zasloff
M
M
Chen
H C
HC
Colamonici
O
O
D000900:Anti-Bacterial Agents; D023181:Antimicrobial Cationic Peptides; D002470:Cell Survival / Q000187:drug effects; D002712:Chlorides / Q000502:physiology; D006096:Gramicidin / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D007473:Ion Channels; D007476:Ionophores; D008564:Membrane Potentials / Q000187:drug effects; D010455:Peptides / Q000633:toxicity*; D011188:Potassium / Q000502:physiology; D012964:Sodium / Q000502:physiology; D014407:Tumor Cells, Cultured / Q000187:drug effects*; D029867:Xenopus Proteins
D000900:Anti-Bacterial Agents; D023181:Antimicrobial Cationic Peptides; D002712:Chlorides; D007473:Ion Channels; D007476:Ionophores; D010455:Peptides; D029867:Xenopus Proteins; C053300:magainin 1 peptide, Xenopus; D006096:Gramicidin; D012964:Sodium; D011188:Potassium