A NOVEL CLASS OF PEPTIDES THAT INDUCE APOPTOSIS AND ABROGATE TUMORIGENESIS IN-VIVO

In testing the ability of certain synthetic peptides of biological ori gin to bind to cell surfaces, we unexpectedly found that they could in duce apoptosis and inhibit tumorigenesis in rodent and human tumor cel l lines. In vitro pre-incubation with the peptides at concentrations a s low as 10(-12) M inhibited tumorigenesis in nude mice, in a dose-dep endent fashion. The inhibition of tumorigenesis was reflected in the r apid induction of apoptosis of tumor cells, pre-incubated with the pep tides, and tested under conditions of anchorage-independence. Inductio n of apoptosis was detectable even at concentrations of 10(-12)-10(-13 ) M (0.1-1.0 pM). Aspecific toxicity of the synthetic peptides was rul ed out by the demonstration that single amino acid substitutions (in a t least 4 peptides) completely abrogated the pro-apoptotic effect, eve n at a concentration of 10(-5) M (10 mu M). (C) 1997 Academic Press.