get out that broccoli and those Brussels sprouts

[Lani]

Unclear whether sulfophorane must be raw or cooked, whether other compounds inactivate it, how much is necessary, but looks like they may be looking into it

: Mol Cancer Ther. 2007 Mar 5; [Epub ahead of print]
Sulforaphane induces cell type-specific apoptosis in human breast cancer cell lines.

Pledgie-Tracy A,
Sobolewski MD,
Davidson NE.
The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, Maryland.
Sulforaphane, an isothiocyanate found in cruciferous vegetables, has been shown to induce phase 2 detoxication enzymes and inhibit the growth of chemically induced mammary tumors in rats, although the exact mechanisms of action of sulforaphane are not understood. In this study, we evaluated the effects of sulforaphane on cell growth and death in several human breast cancer cell lines and examined the hypothesis that sulforaphane acts as a histone deacetylase (HDAC) inhibitor in these cell lines. Sulforaphane treatment inhibited cell growth, induced a G2-M cell cycle block, increased expression of cyclin B1, and induced oligonucleosomal DNA fragmentation in the four human breast cancer cell lines examined, MDA-MB-231, MDA-MB-468, MCF-7, and T47D cells. Activation of apoptosis by sulforaphane in MDA-MB-231 cells seemed to be initiated through induction of Fas ligand, which resulted in activation of caspase-8, caspase-3, and poly(ADP-ribose) polymerase, whereas apoptosis in the other breast cancer cell lines was initiated by decreased Bcl-2 expression, release of cytochrome c into the cytosol, activation of caspase-9 and caspase-3, but not caspase-8, and poly(ADP-ribose) polymerase cleavage. Sulforaphane inhibited HDAC activity and decreased the expression of estrogen receptor-alpha, epidermal growth factor receptor, and human epidermal growth factor receptor-2 in each cell line, although no change in the acetylation of H3 or H4 was seen. These data suggest that sulforaphane inhibits cell growth, activates apoptosis, inhibits HDAC activity, and decreases the expression of key proteins involved in breast cancer proliferation in human breast cancer cells. These results support testing sulforaphane in vivo and warrant future studies examining the clinical potential of sulforaphane in human breast cancer. [Mol Cancer Ther 2007;6(3):1013-21].
PMID: 17339367 [PubMed - as supplied by publisher]

[heblaj01]

According to this piece of research sulforaphane content in broccoli may greatly vary & is always much lower than it is in sprouts.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=16569031&query_hl=1&itool=pubmed_docsum
Evaporative light-scattering analysis of sulforaphane in broccoli samples: Quality of broccoli products regarding sulforaphane contents.

Dr Talalay who ,several years ago sprung the research on broccoli, identified broccoli varieties with superior content & participated in a commercial enterprise to sell them. Some US companies also sell the sprouts or equipment to grow them at home.
I recall a study showing that warming broccoli at 60 degrees Celcius for about 10 minutes maximizes sulforaphane release.

[Lani]

1: Carcinogenesis. 2007 Mar 7; [Epub ahead of print]
Preclinical and Clinical Evaluation of Sulforaphane for Chemoprevention in the Breast.

Cornblatt BS,
Ye L,
Dinkova-Kostova AT,
Erb M,
Fahey JW,
Singh NK,
Chen MS,
Stierer T,
Garrett-Meyer E,
Argani P,
Davidson NE,
Talalay P,
Kensler TW,
Visvanathan K.
Department of Environmental Health Sciences, The Johns Hopkins University, Baltimore, Maryland 21205.
Consumers of higher levels of Brassica vegetables, particularly those of the genus Brassica (broccoli, Brussels sprouts, cabbage), reduce their susceptibility to cancer at a variety of organ sites. Brassica vegetables contain high concentrations of glucosinolates that can be hydrolyzed by the plant enzyme, myrosinase, or intestinal microflora to isothiocyanates, potent inducers of cytoprotective enzymes and inhibitors of carcinogenesis. Oral administration of either the isothiocyanate, sulforaphane, or its glucosinolate precursor, glucoraphanin, inhibits mammary carcinogenesis in rats treated with 7, 12-dimethylbenz[a]anthracene. In this study we sought to determine whether sulforaphane exerts a direct chemopreventive action on animal and human mammary tissue. The pharmacokinetics and pharmacodynamics of a single 150 mumol oral dose of sulforaphane were evaluated in the rat mammary gland. We detected sulforaphane metabolites at concentrations known to alter gene expression in cell culture. Elevated cytoprotective NAD(P)H:quinone oxidoreductase (NQO1) and heme oxygenase-1 (HO-1) gene transcripts were measured using quantitative RT-PCR. An observed 3-fold increase in NQO1 enzymatic activity, as well as 4-fold elevated immunostaining of HO-1 in rat mammary epithelium, provides strong evidence of a pronounced pharmacodynamic action of sulforaphane. In a subsequent pilot study, eight healthy women undergoing reduction mammoplasty were given a single dose of a broccoli sprouts preparation containing 200 mumol of sulforaphane. Following oral dosing, sulforaphane metabolites were readily measurable in human breast tissue enriched for epithelial cells. These findings provide a strong rationale for evaluating the protective effects of a broccoli sprouts preparation in clinical trials of women at risk for breast cancer.
PMID: 17347138 [PubMed - as supplied by publisher]

[Lani]

EGFR and Src are involved in indole-3-carbinol-induced death and cell cycle arrest of human breast cancer cells

Elena P. Moiseeva et al

Indole-3-carbinol (I3C), a dietary chemopreventive compound, induced marked reduction in epidermal growth factor receptor (EGFR) prior to cell death in cells representing three breast cancer subtypes. Signalling pathways, linking these events were investigated in detail. I3C modulated tyrosine phosphorylation from 30 min in four cell lines. In MDA-MB-468 and HBL100 cells, it induced Src activation after 5 h. In MDA-MB-468 cells, I3C induced signalling between 4.5 and 7 h, which involved sequential activation of Src, EGFR, STAT-1 and STAT-3, followed by EGFR degradation. It also induced physical association between activated Src and EGFR. In MCF7 and MDA-MB-231 cells, I3C modulated expression of cell cycle-related proteins, p21Cip1, p27Kip1, cyclin E, cyclin D1 and CDK6, with upregulation of p21Cip1 and cyclin E being dependent on Src. Inhibition of EGFR by specific inhibitors PD153035 or ZD1839 increased susceptibility to I3C-induced apoptosis of MCF7, MDA-MB-468 and MDA-MB-231 cells. Inhibition of Src sensitized MDA-MB-468 and MDA-MB-231 cells to I3C, whereas overexpression of c-Src increased resistance to I3C in MDA-MB-468 and HBL100 cells. Modulation of Src in MDA-MB-468 cells influenced the basal level of EGFR expression and cell viability; the latter being positively correlated with EGFR activation levels. Therefore, EGFR and Src activities are essential for I3C-induced cell cycle arrest and death; however, I3C-induced pathways depend on specific features of breast cancer cells. The cancer types, which rely on ‘EGFR addiction’ or Src deregulation, are likely to be susceptible to I3C.

[Rich66]

Scientists Show How Cruciferous Veggies Stop Breast Cancer

December 29, 2008
by Lynn Shapiro (http://www.dotmed.com/news/search.html?search_author=90788&key=Lynn+Shapiro), Writer
While it has been known for some time that eating cruciferous vegetables, such as broccoli, cauliflower, and cabbage, can help prevent breast cancer, the mechanism by which the active substances in these vegetables inhibit cell proliferation was unknown -- until now.

Scientists in the UC Santa Barbara laboratories of Leslie Wilson, professor of biochemistry and pharmacology, and Mary Ann Jordan, adjunct professor in the Department of Molecular, Cellular, and Developmental Biology, have shown how the healing power of these vegetables works at the cellular level. Their research is published in this month's issue of the journal Carcinogenesis.

"Breast cancer, the second leading cause of cancer death in women, can be protected against by eating cruciferous vegetables such as cabbage and near relatives of cabbage such as broccoli and cauliflower," said first author Olga Azarenko, who is a graduate student at UCSB. "These vegetables contain compounds called isothiocyanates which we believe to be responsible for the cancer-preventive and anti-carcinogenic activities in these vegetables. Broccoli and broccoli sprouts have the highest amount of the isothiocyanates.

"Our paper focuses on the anti-cancer activity of one of these compounds, called sulforaphane, or SFN," Azarenko added. "It has already been shown to reduce the incidence and rate of chemically induced mammary tumors in animals. It inhibits the growth of cultured human breast cancer cells, leading to cell death."

Azarenko made the surprising discovery that SFN inhibits the proliferation of human tumor cells by a mechanism similar to the way that the anticancer drugs taxol and vincristine inhibit cell division during mitosis. (Mitosis is the process in which the duplicated DNA in the form of chromosomes is accurately distributed to the two daughter cells when a cell divides.)

Hundreds of tiny tube-like structures, called microtubules, make up the machinery that cells use to separate the chromosomes. SFN, like the more powerful anticancer agents, interferes with microtubule functioning during mitosis in a similar manner to the more powerful anticancer drugs. However SFN is much weaker than these other plant-based drugs, and thus much less toxic.

"SFN may be an effective cancer preventive agent because it inhibits the proliferation and kills precancerous cells," said Wilson. It is also possible that it could be used as an addition to taxol and other similar drugs to increase effective killing of tumor cells without increased toxicity, Wilson