tailieunhanh - Báo cáo khoa học: Dietary antioxidant curcumin inhibits microtubule assembly through tubulin binding

Curcumin, a component of turmeric, has potent antitumor activity against several tumor types. However, its molecular target and mechanism of anti-proliferative activity are not clear. Here, we identified curcumin as a novel antimicrotubule agent. We have examined the effects of curcumin on cellu-lar microtubules and on reconstituted microtubules in vitro. | ễFEBS Journal Dietary antioxidant curcumin inhibits microtubule assembly through tubulin binding Kamlesh K. Gupta1 Shubhada S. Bharne2 Krishnan Rathinasamy1 Nishigandha R. Naik2 and Dulal Panda1 1 Schoolof Biosciences and Bioengineering Indian Institute of Technology Bombay Powai Mumbai India 2 Biochemistry and Cell Biology CRI ACTREC TMC Kharghar Navi Mumbai India Keywords cell proliferation curcumin microtubule assembly dynamics tubulin Correspondence D. Panda Schoolof Biosciences and Bioengineering Indian Institute of Technology Bombay Powai Mumbai 400 076 India Fax 91 22 2572 3480 Tel 91 22 2576 7838 E-mail panda@ Received 11 July 2006 revised 15 September 2006 accepted 4 October 2006 doi 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 pM and 12 pM respectively. At higher inhibitory concentrations 10 pM 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 pM 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 .