Crotamine toxicity and efficacy in mouse models of melanoma

• Published in: Expert opinion on investigational drugs Vol. 20; no. 9; p. 1189
• Main Authors: Pereira, Alexandre, Kerkis, Alexandre, Hayashi, Mirian A F, Pereira, Aparecida S P, Silva, Fernando S, Oliveira, Eduardo B, Prieto da Silva, Alvaro R B, Yamane, Tetsuo, Rádis-Baptista, Gandhi, Kerkis, Irina
• Format: Journal Article
• Language: English
• Published: England 01.09.2011
• Subjects: Animals; Antineoplastic Agents - therapeutic use; Antineoplastic Agents - toxicity; Cell Line, Tumor; Cell Survival - drug effects; Crotalid Venoms - therapeutic use; Crotalid Venoms - toxicity; Disease Models, Animal; Humans; Melanoma, Experimental - drug therapy; Mice; Mice, Inbred C57BL; Neoplasm Transplantation; Skin Neoplasms - drug therapy
• ISSN: 1744-7658
• DOI: 10.1517/13543784.2011.602064

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. 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. 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. These data warrant further exploration of crotamine as a tumor inhibition compound.