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  • Title: Effective topical treatment of subcutaneous murine B16F10-Nex2 melanoma by the antimicrobial peptide gomesin.
    Author: Rodrigues EG, Dobroff AS, Cavarsan CF, Paschoalin T, Nimrichter L, Mortara RA, Santos EL, Fázio MA, Miranda A, Daffre S, Travassos LR.
    Journal: Neoplasia; 2008 Jan; 10(1):61-8. PubMed ID: 18231639.
    Abstract:
    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.
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