A cyclic peptide, L1AD3, induces early signs of apoptosis in human leukemic T-cell lines

L1AD3 is a small cyclic synthetic peptide designed to resemble the first loop of a cobra venom cytotoxin. Instead of inducing membrane disruption similar to that caused by the parent toxin, L1AD3 promotes extensive and unusually rapid apoptosis in leukemic T‐cells without making the plasma membrane permeable to small fluorescent dyes. Within 4 h, micromolar concentrations of L1AD3 almost totally inhibit thymidine incorporation, and ATP levels decrease significantly. By contrast, normal human white blood cells are not affected by L1AD3, nor is heart cell function affected by it. If L1AD3 kills by interacting with targets that are different from those of currently applied agents, this peptide, or a derivative of it, could become a useful adjunct for cancer chemotherapy. © 2004 Wiley Periodicals, Inc. J Biochem Mol Toxicol 18:204–220, 2004; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/jbt.20025