Contrasting effects of microtubule destabilizers versus stabilizers on induction of death in G1 phase of the cell cycle.

Contrasting effects of microtubule destabilizers versus stabilizers on induction of death in G1 phase of the cell cycle. Biochem Pharmacol. 2018 Dec 19;: Authors: Delgado M, Urbaniak A, Chambers TC Abstract Microtubule targeting agents (MTAs) have been reported to manifest their cytotoxic effects not only in mitosis but also in interphase. However, the relationship between phase-specific susceptibility and MTA concentration, especially with respect to microtubule integrity, remains poorly defined. In addition, whether microtubule stabilizers and destabilizers act similarly or differ in the ability to induce interphase death is unclear. In order to resolve these uncertainties, we report here the results of a systematic comparison of primary acute lymphoblastic leukemia (ALL) and HeLa cells treated with three different MTAs, namely the microtubule stabilizer paclitaxel and two microtubule destabilizers, vincristine, and eribulin. Both types of cells were sensitive to each MTA, with IC50 values in the sub-nanomolar to low nanomolar range. Primary ALL cells arrested in mitosis when treated with paclitaxel at all tested concentrations, whereas the effects of vincristine or eribulin were concentration-dependent; low (< 30 nM) concentrations induced mitotic death whereas higher concentrations (>100 nM) induced death directly in G1 phase. G1 phase death in response to higher concentrations of the destabilizers was associated with compl...
Source: Biochemical Pharmacology - Category: Drugs & Pharmacology Authors: Tags: Biochem Pharmacol Source Type: research