Carcinogenesis Advance Access originally published online on October 23, 2008
Carcinogenesis 2008 29(12):2360-2368; doi:10.1093/carcin/bgn241
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Suppression of microtubule dynamic instability and turnover in MCF7 breast cancer cells by sulforaphane
Department of Molecular, Cellular, and Developmental Biology and the Neuroscience Research Institute, University of California, Santa Barbara, CA 93106, USA
1 Department of Food Science and Human Nutrition, University of Illinois, Urbana, IL 61801, USA
* To whom correspondence should be addressed. Tel: +1 805 893 2819; Fax: +1 805 893 8094; Email: wilson{at}lifesci.ucsb.edu
Sulforaphane (SFN), a prominent isothiocyanate present in cruciferous vegetables, is believed to be responsible along with other isothiocyanates for the cancer preventive activity of such vegetables. SFN 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-green fluorescent protein-
-tubulin breast tumor cells by 
50% (15 µM), SFN 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 concentration required to inhibit mitosis by 50%, SFN 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. SFN 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 SFN in cells is due to a direct effect on the microtubules. The results indicate that SFN 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 SFN's chemopreventive activity.
Abbreviations: GFP, green fluorescent protein; GI50, concentration required to inhibit cell proliferation by 50%; IC50, concentration required to inhibit mitosis by 50%; MAP, microtubule-associated protein; SFN, sulforaphane
Received August 31, 2008; revised October 10, 2008; accepted October 10, 2008.