A novel benzodiazepine derivative that suppresses microtubule dynamics and impairs mitotic progression

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Pirani, Vittoria | Métivier, Mathieu | Gallaud, Emmanuel | Thomas, Alexandre | Ku, Siou | Chrétien, Denis | Ettari, Roberta | Giet, Régis | Corsi, Lorenzo | Benaud, Christelle

Edité par CCSD ; Company of Biologists -

International audience. A novel 2,3-benzodiazepine-4 derivative, named 1g, has recently been shown to function as an anti-proliferative compound. We now show that it perturbs the formation of a functional mitotic spindle, inducing a spindle assembly checkpoint (SAC)-dependent arrest in human cells. Live analysis of individual microtubules indicates that 1g promotes a rapid and reversible reduction in microtubule growth. Unlike most anti-mitotic compounds, we found that 1g does not interfere directly with tubulin or perturb microtubule assembly in vitro The observation that 1g also triggers a SAC-dependent mitotic delay associated with chromosome segregation in Drosophila neural stem cells, suggests that it targets a conserved microtubule regulation module in humans and flies. Altogether, our results indicate that 1g is a novel promising anti-mitotic drug with the unique properties of altering microtubule growth and mitotic spindle organization.

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