BP-M345, a New Diarylpentanoid with Promising Antimitotic Activity

BP-M345,一种具有良好抗有丝分裂活性的新型二芳基戊烷类化合物

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作者:Pedro Novais, Patrícia M A Silva, Joana Moreira, Andreia Palmeira, Isabel Amorim, Madalena Pinto, Honorina Cidade, Hassan Bousbaa

Abstract

Previously, we reported the in vitro growth inhibitory effect of diarylpentanoid BP-M345 on human cancer cells. Nevertheless, at that time, the cellular mechanism through which BP-M345 exerts its growth inhibitory effect remained to be explored. In the present work, we report its mechanism of action on cancer cells. The compound exhibits a potent tumor growth inhibitory activity with high selectivity index. Mechanistically, it induces perturbation of the spindles through microtubule instability. As a consequence, treated cells exhibit irreversible defects in chromosome congression during mitosis, which induce a prolonged spindle assembly checkpoint-dependent mitotic arrest, followed by massive apoptosis, as revealed by live cell imaging. Collectively, the results indicate that the diarylpentanoid BP-M345 exerts its antiproliferative activity by inhibiting mitosis through microtubule perturbation and causing cancer cell death, thereby highlighting its potential as antitumor agent.

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