IDENTIFICATION OF SERUM COMPONENTS THAT INHIBIT THE TUMORICIDAL ACTIVITY OF AMPHIPHILIC ALPHA-HELICAL PEPTIDES

Antimicrobial peptides that can form amphiphilic alpha helices were te sted for their ability to lyse various human tumor cell lines in vitro . These peptides include C18G, whose sequence is a derivative of the c arboxyl terminus of human platelet factor IV, and 399, an idealized am phiphilic alpha helix. Both peptides exhibited potent antitumor activi ty against all cell lines tested, unlike magainin 2, a naturally occur ring antimicrobial peptide of similar structure, which was relatively inactive under the same conditions. Also, the lytic activity of C18G i s specific for tumor cells versus human red blood cells. The effects o f serum can be important when evaluating the potency of lytic peptides , since other tumoricidal peptides have been shown to be completely in activated by low serum levels. Experiments with C18G and 399 revealed that their activity was indeed reduced in the presence of human serum, but that significant lytic activity remained even at relatively high serum concentrations. Various serum components were tested for their i nhibitory activity. Whereas albumin and high-density lipoprotein had o nly slight inhibitory properties, low-density lipoprotein was found to be a potent inhibitor of peptide-mediated cell lysis. The peptide 399 , which is more sensitive to serum inhibition than C18G, also binds mo re extensively to all serum components tested.