Crotamine toxicity and efficacy in mouse models of melanoma

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 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.

Keywords:

• antimicrobial peptides
• cancer cells selective toxicity
• cell-penetrating peptides
• chemotherapeutical compound
• tumor growth arrest

Acknowledgments

The authors thank AS de Souza (Laboratory of Parasitology of Butantan Institute) for his technical assistance with confocal microscopy.

Notes