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Title: Crotamine toxicity and efficacy in mouse models of melanoma
Authors: Pereira, Alexandre
Kerkis, Alexandre
Hayashi, Mirian A. F. [UNIFESP]
Pereira, Aparecida S. P.
Silva, Fernando S.
Oliveira, Eduardo B.
Prieto da Silva, Alvaro R. B.
Yamane, Tetsuo
Radis-Baptista, Gandhi
Kerkis, Irina
Butantan Inst
Vet Act Ltda Genet Aplicada
Virol Lab
Universidade Federal de São Paulo (UNIFESP)
Universidade de São Paulo (USP)
Univ Estado Amazonas
Univ Fed Ceara
Keywords: antimicrobial peptides
cancer cells selective toxicity
cell-penetrating peptides
chemotherapeutical compound
tumor growth arrest
Issue Date: 1-Sep-2011
Publisher: Informa Healthcare
Citation: Expert Opinion On Investigational Drugs. London: Informa Healthcare, v. 20, n. 9, p. 1189-1200, 2011.
Abstract: Objectives: 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.Research design and methods: in vitro cancer cell viability was evaluated after treatment with 1 and 5 mu g/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 mu g/day of crotamine per animal, subcutaneously which was well tolerated; the untreated group received a placebo.Results: Crotamine at 5 mu g/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.
ISSN: 1354-3784
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