Rotenone inhibits mammalian cell proliferation by inhibiting microtubule assembly through tubulin binding

Rotenone HeLa Multipolar spindles
DOI: 10.1111/j.1742-4658.2007.06004.x Publication Date: 2007-08-16T22:29:00Z
ABSTRACT
Rotenone, a widely used insecticide, has been shown to inhibit mammalian cell proliferation and depolymerize cellular microtubules. In the present study, effects of rotenone on assembly microtubules in relation its ability mitosis were analyzed. We found that inhibited HeLa MCF‐7 cells with half maximal inhibitory concentrations 0.2 ± 0.1 µ m 0.4 , respectively. At effective concentration range, depolymerized spindle both types. However, it had much stronger effect interphase compared cells. Rotenone suppressed reassembly living cells, suggesting can suppress microtubule growth rates. Furthermore, reduced intercentrosomal distance at lower range induced multipolar‐spindle formation relatively higher range. It also increased level checkpoint protein BubR1 kinetochore region. GTP hydrolysis rate vitro . binding colchicine tubulin, perturbed secondary structure intrinsic tryptophan fluorescence tubulin extrinsic tubulin−1‐anilinonaphthalene‐8‐sulfonic acid complex, binds tubulin. A dissociation constant 3 0.6 was estimated for tubulin–rotenone complex. The data presented suggest blocks inhibits by perturbing dynamics.
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