TAILIEUCHUNG - Báo cáo khoa học: Rotenone inhibits mammalian cell proliferation by inhibiting microtubule assembly through tubulin binding Pallavi Srivastava and Dulal Panda

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. | ễFEBS Journal Rotenone inhibits mammalian cell proliferation by inhibiting microtubule assembly through tubulin binding Pallavi Srivastava and Dulal Panda Schoolof Biosciences and Bioengineering Indian Institute of Technology Mumbai India Keywords centrosome microtubule assembly dynamics microtubules mitosis rotenone Correspondence D. Panda Schoolof Biosciences and Bioengineering Indian Institute of Technology Bombay Powai Mumbai 400076 India Fax 91 222 572 3480 Tel 91 222 576 7838 E-mail panda@ Received 17 April2007 revised 7 July 2007 accepted 18 July 2007 doi 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 pM and pM 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 .

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