A novel melanoma-targeting peptide screened by phage display exhibits antitumor activity.
Peptide display on the phage surface has been widely used to identify specific peptides targeting several in vivo and in vitro tumor cells and the tumor vasculature, playing a role in the discovery of bioactive antitumor agents. Bioactive peptides have been selected to target important tumor receptors or apoptosis-associated molecules such as p53. Presently, we attempted to identify potentially antitumor bioactive molecules using the whole cell surface as the recognizable static matrix. Such methodology could be advantageous in cancer therapy because it does not require previous characterization of target molecules. Using a C7C phage display library, we screened for peptides binding to the B16F10-Nex2 melanoma cell surface after pre-absorption on melan-A lineage. After a few rounds of enrichment, 50 phages were randomly selected, amplified, and tested for inhibition of tumor cell proliferation. Seven were active, and the corresponding peptide of each phage was chemically synthesized in the cyclic form and tested in vitro. Three peptides were able to preferentially inhibit the melanoma lineage. A unique peptide, [-CSSRTMHHC-], exhibited in vivo antitumor inhibitory activity against a subcutaneous melanoma challenge, rendering 60% of mice without tumor growth. Further, this peptide also markedly inhibited in vitro and in vivo the tumor cell invasion and cell-to-cell adhesiveness in vitro. This is the first report on a bioactive peptide derived from a C7C library active against whole melanoma cells in vitro and in vivo.
Matsuo
Alisson L
AL
Experimental Oncology Unit (UNONEX), Department of Microbiology, Immunology and Parasitology, Federal University of São Paulo, Rua Botucatu 862, oitavo andar, São Paulo, São Paulo 04023-062, Brazil. almatsuo@unifesp.br
Tanaka
Aparecida S
AS
Juliano
Maria A
MA
Rodrigues
Elaine G
EG
Travassos
Luiz R
LR
D000595:Amino Acid Sequence; D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D015820:Cadherins / Q000378:metabolism; D002448:Cell Adhesion / Q000187:drug effects; D045744:Cell Line, Tumor; D019070:Cell Lineage / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D004195:Disease Models, Animal; D004354:Drug Screening Assays, Antitumor; D008545:Melanoma / Q000188:drug therapy*; D008546:Melanoma, Experimental / Q000188:drug therapy; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D009361:Neoplasm Invasiveness; D019151:Peptide Library; D010456:Peptides, Cyclic / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D011485:Protein Binding / Q000187:drug effects; D013194:Staining and Labeling; D040521:Subcutaneous Tissue / Q000187:drug effects / Q000473:pathology; D014410:Tumor Stem Cell Assay
D000970:Antineoplastic Agents; D015820:Cadherins; D019151:Peptide Library; D010456:Peptides, Cyclic
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