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Dietary antioxidant curcumin inhibits microtubule assembly through tubulin binding
Author(s) -
Gupta Kamlesh K.,
Bharne Shubhada S.,
Rathinasamy Krishnan,
Naik Nishigandha R.,
Panda Dulal
Publication year - 2006
Publication title -
the febs journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 204
eISSN - 1742-4658
pISSN - 1742-464X
DOI - 10.1111/j.1742-4658.2006.05525.x
Subject(s) - curcumin , tubulin , microtubule , chemistry , colchicine , microbiology and biotechnology , biochemistry , vinblastine , in vitro , hela , biology , genetics , chemotherapy
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 IC 50 of 13.8 ± 0.7 µ m and 12 ± 0.6 µ m , respectively. At higher inhibitory concentrations (> 10 µ 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 µ 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.