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.