Compound Found in Broccoli Appears to Stop Breast Cancer Cell Growth

URBANA, Ill.--Sulforaphane (SUL), an isothiocyanate derived from hydrolysis of glucoraphanin in broccoli and other cruciferous vegetables, acts to inhibit proliferation of MCF-7 adenocarcinoma cells from the human breast, according to a study published in the September issue of the Journal of Nutrition (134, 9:2229-36, 2004) (www.nutrition.org).

SUL is abundant in such vegetables as broccoli, brussels sprouts and kale. Chewing causes the cell walls of those vegetables to break, and SUL is released into the body.

Keith Singletary, a professor and researcher in phytochemicals and cancer chemoprevention, and doctoral student Steven Jackson, both from the University of Illinois at Urbana-Champaign, exposed cultures of malignant human breast cancer cells to SUL. Within hours, the SUL had blocked cell division and disrupted microtubules, which are essential cell structures needed for the separation of duplicated chromosomes during cell division.

The scientists found treatment of synchronized MCF-7 cells with 15 µmol/L SUL resulted in significant G2/M cell cycle arrest and elevated cyclin B1 protein, within 24 hours. Moreover, 15 µmol/L SUL significantly induced phosphorylation of histone H1, blocked cells in early mitosis and disrupted polymerization of mitotic microtubules in vivo.

This is the first report to show how the naturally occurring plant chemical sulforaphane can block late stages of the cancer process by disrupting components of the cell called microtubules, Singletary said.

Pretty high concentrations of SUL were used in the study, according to Singletary. It is not yet clear whether the doses required to produce inhibition of tubulin polymerization are higher than those achievable via dietary intakes; however, the results show that tubulin disruption may be an important explanation for SULs antiproliferative action, he said.

In addition, in vitro testing showed subsequent exposure of purified bovine brain tubulin to relatively high doses of SUL significantly inhibited both tubulin polymerization rate and total tubulin polymerization. Additionally, polymerization of purified tubulin exposed to isothiocyanate-containing analogs of SUL (other compounds similar to SUL in the isothiocyanate group) was similarly inhibited.

SUL has been shown in past research to induce phase II detoxification enzymes, inhibit chemically-induced mammary tumors in rodents, and induce cell cycle arrest and apoptosis in colon cancer cells.

Whether SUL or the other compounds would cause the same effects in a living animal, we dont know," Singletary said. "However, this does tell us that SUL--at these high doses--does have a mechanism of action that appears to involve disrupting these tubulin proteins from forming polymers.

The scientists concluded 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.