We found a match
Your institution may have rights to this item. Sign in to continue.
- Title
Suppression of microtubule dynamic instability and turnover in MCF7 breast cancer cells by sulforaphane.
- Authors
Olga Azarenko; Tatiana Okouneva; Keith W. Singletary; Mary Ann Jordan; Leslie Wilson
- Abstract
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-α-tubulin breast tumor cells by â¼50% (â¼15 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 SFNs chemopreventive activity.
- Subjects
ANTINEOPLASTIC agents; CANCER prevention; BREAST cancer; MITOSIS regulation; MICROTUBULES; ANTIMITOTIC agents; CANCER cell proliferation
- Publication
Carcinogenesis, 2008, Vol 29, Issue 12, p2360
- ISSN
0143-3334
- Publication type
Article
- DOI
10.1093/carcin/bgn241