Microtubule targeting agents (
MTA) are anti-
cancer molecules that bind
tubulin and interfere with the microtubule functions, eventually leading to cell death. In the present study, we used an in vitro microtubule polymerization assay to screen several
venom families for the presence of anti-microtubule activity. We isolated myotoxin-3, a
peptide of the
crotamine family, and three
isoforms from the
venom of the Northern Pacific rattlesnake Crotalus oreganus oreganus, which was able to increase
tubulin polymerization. Myotoxin-3 turned out to be a
cell-penetrating peptide that slightly diminished the viability of U87
glioblastoma and MCF7
breast carcinoma cells.
Myotoxin 3 also induced remodeling of the U87 microtubule network and decreased MCF-7 microtubule dynamic instability. These effects are likely due to direct interaction with
tubulin. Indeed, we showed that myotoxin-3 binds to
tubulin heterodimer with a Kd of 5.3 µM and stoichiometry of two molecules of
peptide per
tubulin dimer. Our results demonstrate that exogenous
peptides are good candidates for developing new
MTA and highlight the richness of
venoms as a source of pharmacologically active molecules.