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Please use this identifier to cite or link to this item: http://dspace.library.iitb.ac.in/jspui/handle/10054/5175

Title: Rotenone inhibits mammalian cell proliferation by inhibiting microtubule assembly through tubulin binding
Authors: SRIVASTAVA, P
PANDA, D
Keywords: dopaminergic sh-sy5y cells
parkinsons-disease
spindle checkpoint
motor proteins
hela-cells
apoptosis
polymerization
kinetochores
centrosome
dynamics
Issue Date: 2007
Publisher: BLACKWELL PUBLISHING
Citation: FEBS JOURNAL, 274(18), 4788-4801
Abstract: Rotenone, a widely used insecticide, has been shown to inhibit mammalian cell proliferation and to depolymerize cellular microtubules. In the present study, the effects of rotenone on the assembly of microtubules in relation to its ability to inhibit cell proliferation and mitosis were analyzed. We found that rotenone inhibited the proliferation of HeLa and MCF-7 cells with half maximal inhibitory concentrations of 0.2 +/- 0.1 mu M and 0.4 +/- 0.1 mu M, respectively. At its effective inhibitory concentration range, rotenone depolymerized spindle microtubules of both cell types. However, it had a much stronger effect on the interphase microtubules of MCF-7 cells compared to that of the HeLa cells. Rotenone suppressed the reassembly of microtubules in living HeLa cells, suggesting that it can suppress microtubule growth rates. Furthermore, it reduced the intercentrosomal distance in HeLa cells at its lower effective concentration range and induced multipolar-spindle formation at a relatively higher concentration range. It also increased the level of checkpoint protein BubR1 at the kinetochore region. Rotenone inhibited both the assembly and the GTP hydrolysis rate of microtubules in vitro. It also inhibited the binding of colchicine to tubulin, perturbed the secondary structure of tubulin, and reduced the intrinsic tryptophan fluorescence of tubulin and the extrinsic fluorescence of tubulin-1-anilinonaphthalene-8-sulfonic acid complex, suggesting that it binds to tubulin. A dissociation constant of 3 +/- 0.6 mu M was estimated for tubulin-rotenone complex. The data presented suggest that rotenone blocks mitosis and inhibits cell proliferation by perturbing microtubule assembly dynamics.
URI: http://dx.doi.org/10.1111/j.1742-4658.2007.06004.x
http://dspace.library.iitb.ac.in/xmlui/handle/10054/5175
http://hdl.handle.net/10054/5175
ISSN: 1742-464X
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