Effective topical treatment of subcutaneous murine B16F10-Nex2 melanoma by the antimicrobial peptide gomesin.
Gomesin is a potent antimicrobial peptide (AMP) isolated from hemocytes of the spider Acanthoscurria gomesiana. The present study aimed at determining whether gomesin exerted antitumor activity in vitro and in vivo. Topical treatment of subcutaneous murine melanoma with gomesin incorporated in a cream base significantly delayed tumor growth. A direct cytotoxicity of gomesin in murine melanoma B16F10-Nex2 cells and several human tumor cell lineages was observed in vitro, with IC(50) values below 5 microM. The beta-hairpin structure of gomesin with disulfide bridges seemed essential for optimal activity. d-Gomesin was equally active. A membrane-permeabilizing activity was suggested, as gomesin bound to the cell membrane and cytoplasmic lactate dehydrogenase was detected extracellularly. At doses causing partial growth of tumor cells, gomesin allowed internalization of macromolecules (immunoglobulins), which increased the cytotoxic effect. The in vivo antitumor effect of gomesin might also involve a cytotoxic effect on endothelial cells because cultured human endothelial cells were killed in vitro at a similar concentration range. This effect represents a novel and potential use for gomesin as a topical agent against unsuccessfully treated intradermal and epithelial skin cancers. To our knowledge, this is the first report on the successful topical use of AMPs in cancer treatment.
Rodrigues
Elaine G
EG
Experimental Oncology Unit (UNONEX), Federal University of São Paulo (UNIFESP), São Paulo, Brazil. rodrigues.elaine@unifesp.br
Dobroff
Andrey Ss
AS
Cavarsan
Clarissa F
CF
Paschoalin
Thaysa
T
Nimrichter
Leonardo
L
Mortara
Renato A
RA
Santos
Edson Lucas
EL
Fázio
Marcos A
MA
Miranda
Antonio
A
Daffre
Sirlei
S
Travassos
Luiz R
LR
D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000378:metabolism; D002463:Cell Membrane Permeability; D049109:Cell Proliferation / Q000187:drug effects; D019069:Cell Respiration / Q000187:drug effects; D042783:Endothelial Cells / Q000187:drug effects; D004912:Erythrocytes / Q000187:drug effects; D006801:Humans; D008264:Macrophages / Q000187:drug effects; D008546:Melanoma, Experimental / Q000188:drug therapy* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D015394:Molecular Structure; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000473:pathology; D040521:Subcutaneous Tissue
D023181:Antimicrobial Cationic Peptides; D000970:Antineoplastic Agents; C415987:gomesin