Carcinogenesis Advance Access published online on October 23, 2008
Carcinogenesis, doi:10.1093/carcin/bgn241
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Suppression of microtubule dynamic instability and turnover in MCF7 breast cancer cells by sulforaphane
1 Department of Molecular, Cellular, and Developmental Biology and the Neuroscience Research Institute, University of California, Santa Barbara, CA 93106
2 Department of Food Science and Human Nutrition, University of Illinois, Urbana, IL 61801
* To whom correspondence should be addressed. Phone: 805-893-2819, fax: 805-893-8094, e-mail: wilson{at}lifesci.ucsb.edu
Sulforaphane, a prominent isothiocyanate present in cruciferous vegetables, is believed to be responsible along with other isothiocyanates for the cancer preventive activity of such vegetables. Sulforaphane arrests mitosis, possibly by affecting spindle microtubule function. A critical property of microtubules is their rapid and time-sensitive growth and shortening dynamics (dynamic instability), and suppression of dynamics by antimitotic anticancer drugs (e.g., taxanes and the vinca alkaloids) is central to the anticancer mechanisms of such drugs. We found that at concentrations that inhibited proliferation and mitosis of MCF7-GFP-
-tubulin breast tumor cells by 
50% (15 µM), sulforaphane significantly modified microtubule organization in arrested spindles without modulating the spindle microtubule mass, in a manner similar to that of much more powerful antimitotic drugs. By using quantitative fluorescence video microscopy, we determined that at its mitotic IC50, sulforaphane suppressed the dynamic instability of the interphase microtubules in these cells, strongly reducing the rate and extent of growth and shortening and decreasing microtubule turnover, without affecting the polymer mass. Sulforaphane suppressed the dynamics of purified microtubules in a similar fashion at concentrations well below those required to depolymerize microtubules, indicating that the suppression of dynamic instability by sulforaphane in cells is due to a direct effect on the microtubules. The results indicate that sulforaphane arrests proliferation and mitosis by stabilizing microtubules in a manner weaker than but similar to more powerful clinically used antimitotic anticancer drugs, and strongly support the hypothesis that inhibition of mitosis by microtubule stabilization is important for sulforaphane's chemopreventive activity.
Key Words: Sulforaphane • isothiocyanates • microtubule dynamics • microtubule turnover • mitosis • MCF7 cells
Received August 31, 2008; revised October 10, 2008; accepted October 10, 2008.