Myotoxin-3 from the Pacific Rattlesnake Crotalus oreganus oreganus Venom Is a New Microtubule-Targeting Agent - Archive ouverte HAL Access content directly
Journal Articles Molecules Year : 2022

Myotoxin-3 from the Pacific Rattlesnake Crotalus oreganus oreganus Venom Is a New Microtubule-Targeting Agent

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Caroline Radix
  • Function : Author
  • PersonId : 1193726
Claude Villard
Gilles Breuzard
Pascale Barbier
Harold de Pomyers
  • Function : Author
  • PersonId : 1193728
Didier Gigmes
  • Function : Author
  • PersonId : 956680
François Devred
Hervé Kovacic
Kamel Mabrouk
  • Function : Author
  • PersonId : 1140914
José Luis

Abstract

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.
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Dates and versions

hal-03870782 , version 1 (24-11-2022)
hal-03870782 , version 2 (05-12-2022)

Licence

Attribution - CC BY 4.0

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Cite

María Cecilia González García, Caroline Radix, Claude Villard, Gilles Breuzard, Pascal Mansuelle, et al.. Myotoxin-3 from the Pacific Rattlesnake Crotalus oreganus oreganus Venom Is a New Microtubule-Targeting Agent. Molecules, In press, 27, ⟨10.3390/molecules27238241⟩. ⟨hal-03870782v2⟩
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