Suppression of Microtubule Dynamic Instability and Turnover in MCF7 Breast Cancer Cells by Sulforaphane
Suppression of microtubule dynamic instability and turnover in MCF7 breast cancer cells by sulforaphane.
Carcinogenesis. 2008 Dec;29(12):2360-8. Epub 2008 Oct 23.
Azarenko O, Okouneva T, Singletary KW, Jordan MA, Wilson L.
Department of Molecular, Cellular, and Developmental Biology and the Neuroscience Research Institute, University of California, Santa Barbara, CA 93106, USA.
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-alpha-tubulin breast tumor cells by approximately 50% (~15 microM), 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 sulforaphane arrests proliferation and mitosis by stabilizing microtubules in a manner weaker than but similar to more powerful clinically used antimitotic anticancer drugsand strongly support the hypothesis that inhibition of mitosis by microtubule stabilization is important for SFN’s chemopreventive activity.
Note from ISS: Several crucifer sprouts including broccoli sprouts are currently the most potent natural source of sulforaphane known. They often produce 10 to 100 times the amount of sulforaphane as their corresponding mature vegetables. (“Broccoli sprouts: an exceptionally rich source of inducers of enzymes that protect against chemical carcinogens.”, Proc Natl Acad Sci U S A 1997 Sep 16;94(19):10367-72.)