TAILIEUCHUNG - Báo cáo khoa học: Curcumin suppresses the dynamic instability of microtubules, activates the mitotic checkpoint and induces apoptosis in MCF-7 cells

In this study, curcumin, a potential anticancer agent, was found to dampen the dynamic instability of individual microtubules in living MCF-7 cells. It strongly reduced the rate and extent of shortening states, and modestly reduced the rate and extent of growing states. In addition, curcumin decreased the fraction of time microtubules spent in the growing state and strongly increased the time microtubules spent in the pause state. | ỊFEBS Journal Curcumin suppresses the dynamic instability of microtubules activates the mitotic checkpoint and induces apoptosis in MCF-7 cells Mithu Banerjee Parminder Singh and Dulal Panda Department of Biosciences Bioengineering Indian Institute of Technology Bombay Mumbai India Keywords apoptosis BubR1 combination study delayed mitosis dynamic instability Correspondence D. Panda Department of Biosciences Bioengineering Indian Institute of Technology Bombay Powai Mumbai-400076 India Fax 91 222 572 3480 Tel 91 222 576 7838 7770 E-mail panda@ Received 14 April2010 revised 21 May 2010 accepted 24 June 2010 doi In this study curcumin a potential anticancer agent was found to dampen the dynamic instability of individual microtubules in living MCF-7 cells. It strongly reduced the rate and extent of shortening states and modestly reduced the rate and extent of growing states. In addition curcumin decreased the fraction of time microtubules spent in the growing state and strongly increased the time microtubules spent in the pause state. Brief treatment with curcumin depolymerized mitotic microtubules perturbed microtubule-kinetochore attachment and disturbed the mitotic spindle structure. Curcumin also perturbed the localization of the kinesin protein Eg5 and induced monopolar spindle formation. Further curcumin increased the accumulation of Mad2 and BubRl at the kinetochores indicating that it activated the mitotic checkpoint. In addition curcumin treatment increased the metaphase anaphase ratio indicating that it can delay mitotic progression from the metaphase to anaphase. We provide evidence suggesting that the affected cells underwent apoptosis via the p53-depen-dent apoptotic pathway. The results support the idea that kinetic stabilization of microtubule dynamics assists in the nuclear translocation of p53. Curcumin exerted additive effects when combined with vinblastine a microtubule depolymerizing drug whereas the .

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