A Novel Class of Peptides That Induce Apoptosis and Abrogate Tumorigenesisin Vivo

Abstract

In testing the ability of certain synthetic peptides of biological origin to bind to cell surfaces, we unexpectedly found that they could induce apoptosis and inhibit tumorigenesis in rodent and human tumor cell lines. In vitro pre-incubation with the peptides at concentrations as low as 10−12M inhibited tumorigenesis in nude mice, in a dose-dependent fashion. The inhibition of tumorigenesis was reflected in the rapid induction of apoptosis of tumor cells, pre-incubated with the peptides, and tested under conditions of anchorage-independence. Induction of apoptosis was detectable even at concentrations of 10−12–10−13M (0.1-1.0 pM). Aspecific toxicity of the synthetic peptides was ruled out by the demonstration that single amino acid substitutions (in at least 4 peptides) completely abrogated the pro-apoptotic effect, even at a concentration of 10−5M (10 μM).