The present study was designed to investigate the mechanism by which the cruciferous vegetable compound benzyl isothiocyanate suppresses the viability of human breast cancer cells. Benzyl isothiocyanate has been shown to inhibit the growth of both hormone receptor positive MCF-7 and hormone receptor negative MDA-MB-231 human breast cancer cells and also to retard mammary cancer development in MMTV-neu mice by causing apoptosis. However, but the mechanism of cell death is not fully understood. The authors show that whereas p53 is not required for benzyl isothiocyanate-induced cell death, proapoptotic response to benzyl isothiocyanate is mediated by suppression of X-linked inhibitor of apoptosis (XIAP) protein expression. Benzyl isothiocyanate treatment heightened levels of total and Ser15-phosphorylated p53 protein in MCF-7 breast cancer cells, but the proapoptotic response to benzyl isothiocyanate remained even after knockdown of the p53 protein level. In both MCF-7 and MDA-MB-231 cells, exposure to benzyl isothiocyanate caused in a marked decrease in protein level of XIAP as soon as eight hours after treatment. Ectopic expression of XIAP was found to confer statistically significant protection against benzyl isothiocyanate-mediated cytoplasmic histone-associated apoptotic DNA fragmentation in both breast cancer cell types. In addition, inhibition of implanted MDA-MB-231 cell growth in female athymic mice by benzyl isothiocyanate administration was related to a modest but statistically significant decrease in XIAP protein level. The benzyl isothiocyanate treatment also was found to cause induction as well as nuclear translocation of survivin only in the MCF-7 cells. Furthermore, the benzyl isothiocyanate-induced apoptosis was modestly but statistically significantly augmented by RNA interference of survivin in MCF-7 breast cancer cells. The authors comment that their study provides new insight into the molecular mechanism of benzyl isothiocyanate-induced apoptosis. In particular, suppression of XIAP expression is a critical mediator of this process.

Sulforaphane [1-isothiocyanato-4-(methylsulfinyl)butane] is an isothiocyanate in cruciferous vegetables with a number of potential chemopreventive actions. The current study examined the effects of sulforaphane on the proliferation of human MCF-7 breast cancer cells and on the expression of estrogen receptor α (ERα) protein and mRNA in the cells. Sulforaphane was found to inhibit cell proliferation and ERα protein expression. Lowered ERα expression was also found to be accompanied by decreased progesterone receptor expression. MCF-7 cell mRNA expression was inhibited by sulforaphane at relatively high doses, but not at low sulforaphane concentrations. The authors conclude that sulforaphane can inhibit proliferation of MCF-7 breast cancer cells and down-regulation of hormone receptor expression.

Indole-3-carbinol, a phytochemical derived from cruciferous vegetables such as broccoli and brussels sprouts, is a powerful antiproliferative in human breast cancer cells and can decrease metastatic spread of tumors in experimental animals. The current study demonstrated that indole-3-carbinol significantly decreased the in vitro migration of MDA-MB-231 breast cancer cells, a highly invasive cell line. The data demonstrated that indole-3-carbinol induces stress fibers and peripheral focal adhesions and that this leads to a reduction in motility of human breast cancer cells.

The current study was designed to find out if the chemopreventive effects of brussels sprouts seen in epidemiological studies are due in part to protection against DNA damage. After administering brussels sprouts, a decrease of the endogenous formation of oxidized bases and a lowering of DNA damage caused by hydrogen peroxide was observed. These effects could not be explained bythe actions of antioxidant enzymes glutathione peroxidase and superoxide dismutase; however, in vitro experiments indicate that brussels sprouts contain compounds that act as direct scavengers of reactive oxygen species. The authors conclude that brussels sprout consumption leads to inhibition of sulfotransferases in humans and protection against PhIP and oxidative DNA damage.

The present study was designed to investigate molecular mechanisms behind the beneficial effects of brussels sprout consumption using a pilot dietary intervention study with five participants. After the dietary intervention, there was a significant up-regulation of the synthesis of manganese superoxide dismutase as well as significant down-regulation of the synthesis of heat shock 70 kDa protein in the participants' white blood cells. Both these proteins play a role in malignant transformation of cells. The findings indicate that the changes in the synthesis of these proteins may be involved in the chemopreventive effects of cruciferous vegetables.

The major glucosinolates in broccoli (glucoiberin, glucoraphanin, and glucobrassicin) were found to be greatly reduced by both water and steam blanching. Water blanching produced the most significant loss of glucosinolates. However, blanching brussels sprouts did not produce this significant reduction of glucosinolates, apparently because of the structure brussels sprouts (a tight, compact vegetable that is more resistant to the leaching effects of blanching).

Based on epidemiologic evidence, high dietary intake of brassica vegetables such as broccoli, cabbage, and brussels sprouts protects against tumorigenesis in multiple organs. Previously, the authors showed that 3,3'-Diindolylmethane, one of the active compounds derived from brassica vegetables, induced cell cycle arrest in human breast cancer MCF-7 cells by a mechanism that included increased expression of p21. In the present study, the events leading to p21 overexpression were further investigated. The study establishes the critical role of enhanced mitochondrial ROS release in 3,3'-diindolylmethane-induced p21 up-regulation in human breast cancer cells.

Indole-3-carbinol, a component of cruciferous vegetables, has been shown to be cancer chemopreventive in liver, colon, and mammary tissue when given before or at the same time as exposure to a carcinogen. However there has been some reported evidence that consumption of indole-3-carbinol after carcinogen exposure might promote tumors in some tissues. The present study was designed to examine whether indole-3-carbinol acts as a tumor promoter in female Sprague-Dawley rats after carcinogen exposure. Ninety-six rats were divided into five study groups. The animals of groups 1, 2 and 3 received an intraperitoneal injection of MNU (a potent carcinogen) at the age of 50 days whereas the animals of groups 4 and 5 were injected with saline only. Animals of groups 1 and 2 were given diets containing 100 ppm and 300 ppm indole-3-carbinol respectively from week 1 until week 25 after MNU treatment. The animals of group 4 were given basal diet containing 300 ppm indole-3-carbinol (without MNU treatment). The incidences of mammary tumors in the groups 1, 2 and 3 were 95.8%, 83.3% and 82.4%, respectively. The average number of tumors in the tumor bearing rats of the MNU and indole-3-carbinol 300 ppm group (group 2; 3.85+/-0.63) was higher than that in the MNU alone group (group 3; 2.46+/-0.31). The authors conclude that exposure to indole-3-carbinol after carcinogen treatment did not suppress development of mammary tumors.

Cruciferous vegetable extracts from freeze-dried cabbage, freeze-dried fermented cabbage, and acidified brussels sprouts were prepared by exhaustive extraction with ethyl acetate. Estrogenic and antiestrogenic effects of these extracts were analyzed. To determine whether the extracts are potential estrogen receptor (ER) ligands that can act as agonists or antagonists, the binding affinity of extracts for the ER was measured. The extracts were found to bind with low affinity to the ER, and the relative binding affinity ranking was estradiol > freeze-dried fermented cabbage > freeze-dried cabbage > acidified brussels sprouts. The extracts were then evaluated for their estrogenic and antiestrogenic activities in estrogen-dependent human breast cancer (MCF-7) cells. At low concentrations, all of the extracts reduced estradiol-induced MCF-7 cell proliferation. At higher extract concentrations, however, the extracts increased proliferation in MCF-7 cells. Similarly, expression of the pS2 gene was induced by higher extract concentrations. The pure estrogen antagonist ICI 182,780 suppressed the cell proliferation induced by the extracts as well as by estradiol and also the induction of pS2 expression by the extracts. Growth of the ER-negative MDA-231 breast cancer cells was not affected by the extracts or by estradiol. The authors conclude that cruciferous vegetable extracts act bifunctionally, like an antiestrogen at low concentrations and an estrogen agonist at high concentrations.

Previous studies indicate that the estrogen metabolite 16alpha-hydroxyestrone acts as a breast cancer promoter. The alternative product of estrogen metabolism, 2-hydroxyestrone, does not exhibit estrogenic properties in breast tissue. Therefore, low values of the ratio 2-hydroxyestrone to 16alpha-hydroxyestrone (2:16) in urine may be a marker for greater breast cancer risk. Brassica vegetables such as broccoli may shift estrogen metabolism and increase the 2:16 ratio. In the current study, 34 healthy postmenopausal women participated in an intensive intervention designed to facilitate the addition of brassica vegetables to the daily diet. With adjustment for other dietary parameters, brassica vegetable consumption was associated with a statistically significant increase in 2:16 values. The authors conclude that to the extent that the 2:16 ratio is associated with breast cancer risk, future research should consider brassica vegetable consumption as a potentially effective dietary strategy to prevent breast cancer.

Ten healthy subjects were given 20 mg of warfarin before and after a daily intake of 400 g of brussels sprouts for two weeks. The brussels sprouts diet increased warfarin disposal, as shown by a 29% increase in mean elimination, accompanied by a 27% increase in metabolic clearance and a 16% decrease in plasma AUC. The authors conclude that a high intake of brussels sprouts accelerates warfarin disposal and thereby might result in less anticoagulation.