A novel class of peptides that induce apoptosis and abrogate tumorigenesis in vivo.
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(-12) M 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(-13) M (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(-5) M (10 microM).
Resnicoff
M
M
Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA. resnicol@jeflin.tju.edu
Huang
Z
Z
Herbert
D
D
Abraham
D
D
Baserga
R
R
D019943:Amino Acid Substitution; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D005260:Female; D005909:Glioblastoma / Q000473:pathology / Q000517:prevention & control; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009842:Oligopeptides / Q000138:chemical synthesis / Q000494:pharmacology* / Q000633:toxicity; D010051:Ovarian Neoplasms / Q000473:pathology / Q000517:prevention & control; D051381:Rats; D013045:Species Specificity; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D009842:Oligopeptides