Sulforaphane Inhibits Human MCF-7 Mammary Cancer Cell Mitotic Progression and Tubulin Polymerization1,2

Sulforaphane (SUL), an isothiocyanate derived from hydrolysis of glucoraphanin in broccoli and other cruciferous vegetables, was shown to induce phase II detoxification enzymes, inhibit chemically induced mammary tumors in rodents, and more recently, to induce cell cycle arrest and apoptosis in colo...

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Bibliographic Details
Published inThe Journal of nutrition Vol. 134; no. 9; p. 2229
Main Authors Jackson, Steven J T, Singletary, Keith W
Format Journal Article
LanguageEnglish
Published Bethesda American Institute of Nutrition 01.09.2004
Subjects
Breast cancer
Cell cycle
Cell division
Nutrition
Polymerization
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Summary:Sulforaphane (SUL), an isothiocyanate derived from hydrolysis of glucoraphanin in broccoli and other cruciferous vegetables, was shown to induce phase II detoxification enzymes, inhibit chemically induced mammary tumors in rodents, and more recently, to induce cell cycle arrest and apoptosis in colon cancer cells. In the present study, we demonstrate that SUL also acts to inhibit proliferation of MCF-7 adenocarcinoma cells from the human breast. Treatment of synchronized MCF-7 cells with 15 µmol/L SUL resulted in significant (P < 0.05) G^sub 2^/M cell cycle arrest (167% of control) and elevated cyclin B1 protein (175% of control) within 24 h. Moreover, 15 µmol/L SUL significantly (P < 0.05) induced phosphorylation of histone H1 (167% of control), blocked cells in early mitosis (~10-fold increase over control), and disrupted polymerization of mitotic microtubules in vivo. Subsequent exposure of purified bovine brain tubulin to relatively high doses of SUL significantly (P < 0.05) inhibited both tubulin polymerization rate (51% of control) and total tubulin polymerization (78% of control) in vitro. Additionally, polymerization of purified tubulin exposed to isothiocyanate-containing analogs of SUL was similarly inhibited. Taken together, these findings indicate that SUL has mammary cancer suppressive actions involving mitotic cell cycle arrest and suggest a mechanism linked to the disruption of normal tubulin polymerization and/or more subtle effects on microtubule dynamics. [PUBLICATION ABSTRACT] KEY WORDS: * mitotic arrest * microtubule polymerization * human mammary carcinoma
ISSN:0022-3166
1541-6100