Anti-tumor activity of synthetic peptide fragments of the human interferon-alpha 2.
We have studied an influence of nine overlapping peptides from the region between amino acid residues 124 and 144 of the human interferon (FIN)-alpha 2 molecule on the growth of human lymphoid tumor cell lines in vitro. It was found that several, but not all, synthetic peptides inhibited proliferation of the same cell lines that IFN did. One of peptides, corresponding to the 124-138 amino acid residues of the IFN molecule (124-138) was most active. Using a human-mouse somatic hybrid cell line, we have shown that antiproliferative activity of the peptide 124-138 and IFN depended on the presence of human chromosome 21. Receptor binding studies also demonstrated that the peptide specifically interacted with membrane receptors on hybrid human-mouse cells carrying human chromosome 21, but not on parental mouse cells. Displacement experiments confirm that IFN and the peptide 124-138 compete for the same binding sites. Taken together, the data presented support a hypothesis that the C-terminal part of the IFN molecule contributes to antiproliferative activity possessed by IFN. Synthetic peptides studied in the present work may serve as a tool for studying tumor cell growth regulation by IFN and may be considered as potential nontoxic anti-tumor agents.
Danilkovitch
A
A
Department of Cellular Physiology and Immunology, Biological Faculty, Moscow State University, Russian Federation.
Freze
K
K
Romashkova
J
J
Makarov
E
E
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D001665:Binding Sites; D002455:Cell Division / Q000187:drug effects; D002891:Chromosomes, Human, Pair 21; D006801:Humans; D006822:Hybrid Cells; D066298:In Vitro Techniques; D016898:Interferon-alpha / Q000737:chemistry / Q000494:pharmacology*; D051379:Mice; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000494:pharmacology*; D011956:Receptors, Cell Surface / Q000378:metabolism; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D016898:Interferon-alpha; D010446:Peptide Fragments; D011956:Receptors, Cell Surface