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Published on: September 7, 2013
Crotamine toxicity and efficacy in mouse models of melanoma
Alexandre Pereira1, Alexandre Kerkis, Mirian A F Hayashi
1Butantan Institute, Laboratory of Genetics, Sao Paulo, SP, Brazil.
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.
Insights
Crotamine demonstrates potent anticancer activity, effectively eliminating cancer cells in vitro and significantly inhibiting tumor growth and improving survival rates in mice. Further research into crotamine as a tumor inhibition compound is warranted.
Area of Science:
- Biochemistry
- Pharmacology
- Oncology
Background:
- Antimicrobial peptides (AMPs) and cell-penetrating peptides (CPPs) exhibit selective anticancer activity.
- Crotamine shares functional similarities with both AMPs and CPPs, suggesting potential anticancer properties.
Purpose of the Study:
- To investigate the in vitro and in vivo anticancer toxicity of crotamine.
- To evaluate crotamine's efficacy in inhibiting tumor growth and improving survival in a murine melanoma model.
Main Methods:
- In vitro assessment of cancer cell viability after crotamine treatment (1 and 5 μg/ml).
- In vivo study using C57Bl/6J mice with B16-F10 cutaneous melanoma, comparing crotamine (1 μg/day) to placebo over 21 days.
Main Results:
- Crotamine (5 μg/ml) was cytotoxic to B16-F10, Mia PaCa-2, and SK-Mel-28 cancer cells, sparing normal cells.
- In vivo, crotamine significantly delayed tumor implantation, inhibited tumor growth (average weight reduced from 4.60g to 0.27g), and increased survival rates (30/35 vs 7/35 mice).
Conclusions:
- Crotamine exhibits significant anticancer effects both in vitro and in vivo.
- These findings support further investigation of crotamine as a potential therapeutic agent for tumor inhibition.
