title: Crotamine toxicity and efficacy in mouse models of melanoma.
abstract: OBJECTIVE
  Selective anticancer cell activity for both cell-penetrating and cationic antimicrobial peptides has previously been reported. As crotamine possesses activities similar to both of these, this study investigates crotamine's anticancer toxicity in vitro and in vivo.
  
  
  METHODS
  In vitro cancer cell viability was evaluated after treatment with 1 and 5 μg/ml of crotamine. In vivo crotamine cytotoxic effects in C57Bl/6J mice bearing B16-F10 primary cutaneous melanoma were tested, with two groups each containing 35 mice. The crotamine-treated group received 1 μg/day of crotamine per animal, subcutaneously which was well tolerated; the untreated group received a placebo.
  
  
  RESULTS
  Crotamine at 5 μg/ml was lethal to B16-F10, Mia PaCa-2 and SK-Mel-28 cells and inoffensive to normal cells. In vivo crotamine treatment over 21 days significantly delayed tumor implantation, inhibited tumor growth and prolonged the lifespan of the mice. Mice in the crotamine-treated group survived at significantly higher rates (n = 30/35) than those in the untreated group (n = 7/35) (significance calculated with the Kaplan-Meier estimator). The average tumor weight in the untreated group was 4.60 g but was only about 0.27 g in the crotamine-treated mice, if detectable.
  
  
  CONCLUSIONS
  These data warrant further exploration of crotamine as a tumor inhibition compound.
authors.affiliation: Butantan Institute, Laboratory of Genetics, Sao Paulo, SP, Brazil.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Pereira
authors.forename: Alexandre
authors.initials: A
authors.lastname: Kerkis
authors.forename: Mirian A F
authors.initials: MA
authors.lastname: Hayashi
authors.forename: Aparecida S P
authors.initials: AS
authors.lastname: Pereira
authors.forename: Fernando S
authors.initials: FS
authors.lastname: Silva
authors.forename: Eduardo B
authors.initials: EB
authors.lastname: Oliveira
authors.forename: Alvaro R B
authors.initials: AR
authors.lastname: Prieto da Silva
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Yamane
authors.forename: Gandhi
authors.initials: G
authors.lastname: Rádis-Baptista
authors.forename: Irina
authors.initials: I
authors.lastname: Kerkis
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use* / Q000633:toxicity; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D003435:Crotalid Venoms / Q000627:therapeutic use* / Q000633:toxicity; D004195:Disease Models, Animal; D006801:Humans; D008546:Melanoma, Experimental / Q000188:drug therapy*; D051379:Mice; D008810:Mice, Inbred C57BL; D009368:Neoplasm Transplantation; D012878:Skin Neoplasms / Q000188:drug therapy*
chemical_list: D000970:Antineoplastic Agents; D003435:Crotalid Venoms; C010563:crotamine