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Please use this identifier to cite or link to this item: http://dspace.library.iitb.ac.in/jspui/handle/10054/5162

Title: Dietary antioxidant curcumin inhibits microtubule assembly through tubulin binding
Authors: GUPTA, KK
BHARNE, SS
RATHINASAMY, K
NAIK, NR
PANDA, D
Keywords: endogenous mammalian metabolite
chemopreventive agents
cell-proliferation
antitumor action
cancer cells
polymerization
dynamics
site
apoptosis
2-methoxyestradiol
Issue Date: 2006
Publisher: BLACKWELL PUBLISHING
Citation: FEBS JOURNAL, 273(23), 5320-5332
Abstract: Curcumin, a component of turmeric, has potent antitumor activity against several tumor types. However, its molecular target and mechanism of antiproliferative activity are not clear. Here, we identified curcumin as a novel antimicrotubule agent. We have examined the effects of curcumin on cellular microtubules and on reconstituted microtubules in vitro. Curcumin inhibited HeLa and MCF-7 cell proliferation in a concentration-dependent manner with IC50 of 13.8 +/- 0.7 mu M and 12 +/- 0.6 mu M, respectively. At higher inhibitory concentrations (> 10 mu M), curcumin induced significant depolymerization of interphase microtubules and mitotic spindle microtubules of HeLa and MCF-7 cells. However, at low inhibitory concentrations there were minimal effects on cellular microtubules. It disrupted microtubule assembly in vitro, reduced GTPase activity, and induced tubulin aggregation. Curcumin bound to tubulin at a single site with a dissociation constant of 2.4 +/- 0.4 mu M and the binding of curcumin to tubulin induced conformational changes in tubulin. Colchicine and podophyllotoxin partly inhibited the binding of curcumin to tubulin, while vinblastine had no effect on the curcumin-tubulin interactions. The data together suggested that curcumin may inhibit cancer cells proliferation by perturbing microtubule assembly dynamics and may be used to develop efficacious curcumin analogues for cancer chemotherapy.
URI: http://dx.doi.org/10.1111/j.1742-4658.2006.05525.x
http://dspace.library.iitb.ac.in/xmlui/handle/10054/5162
http://hdl.handle.net/10054/5162
ISSN: 1742-464X
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