1. Identification & Isolation of the Chemoprotective Substances in Cruciferous Vegetables

3. “ If a cancerous ulcer appears upon the breasts, apply a crushed cabbage leaf and it will make it well.” Cato the Elder (Rome: 234-149 BC) [first recorded description of these plants as Brassica = cabbage]

5. “ I do not like broccoli. And I haven't liked it since I was a little kid and my mother made me eat it. I’m the president of the United States and I’m not going to eat any more broccoli.” George Bush 41st President of the U.S.

6. Consumption of 19 vegetables including sauerkraut, coleslaw, Brussels sprouts and broccoli Meta-analysis: Crucifer consumption and cancer risk Adapted from: Graham et al. (1978) JNCI 61:709-714 Kohlmeier & Su (1997) FASEB J. 11: A369 OR (Odds Ratio) servings/month grams/day

8. Cruciferae (Brassicaceae) Arabidopsis (thule cress) Brassica Eruca (Arugula) Raphanus (radish; daikon) Nasturtium (watercress) (incl. mustard greens, Canola, rutabaga, Chinese cabbage, collards, turnip) oleracea botrytis (cauliflower) capitata (cabbage) gemmifera (Brussels sprouts) italica (broccoli)

10. Estimated Glucosinolate Intake Estimates of average per person daily intake of dietary glucosinolates range from 15-18 mg in Canada & U.S 22 mg in the Netherlands 30-50 mg in the UK 112 mg in Japan 1 Milford & Evans (1991) Outlook on Agriculture 20:31-37. 2 Mullin & Sahasrabudhe (1978) Nutr. Rep. Intl. 18:273-279. 3 Wattenberg et al. (1986) In Diet, Nutrition & Cancer , Eds. Hayashi et al.

22. Int J Oncol. 2005 Nov;27(5):1391-9. Indole-3-carbinol inhibits the growth of human colon carcinoma cells but enhances the tumor multiplicity and volume of azoxymethane-induced rat colon carcinogenesis. Suzui M , Inamine M , Kaneshiro T , Morioka T , Yoshimi N , Suzuki R , Kohno H , Tanaka T . Tumor Pathology Division, Faculty of Medicine, University of the Ryukyus, Okinawa 903-0215, Japan. suzui@med.u-ryukyu.ac.jp Indole-3-carbinol (I3C) is a naturally occurring phytochemical which exerts a broad range of biological activities. The purpose of this study was to examine the effects of I3C on colon carcinogenesis, cell proliferation, cell-cycle progression and apoptosis, and on the levels of expression of several cell-cycle control molecules. We used a long-term rat model by using azoxymethane (AOM) to induce tumors (adenomas and adenocarcinomas) in the colon. In the present study, we found that after AOM injection, the treatment of male F344 rats with 0.01 and 0.05% I3C caused a significant increase in the tumor multiplicity of adenocarcinomas by 2.2- (P<0.05 for 0.01% I3C) and 2.1-fold (P<0.0002 for 0.05% I3C) respectively, when compared to the control rats. In addition, the tumor multiplicity of adenoma plus adenocarcinoma and the volume of adenocarcinoma were also increased by 2.0- (P<0.00001) and 2.1-fold (P<0.05) respectively, compared to the control. I3C significantly increased the proliferating cell nuclear antigen labeling index (PCNA LI) (P<0.008) and decreased the apoptotic index (P<0.05) of the colon adenocarcinoma. In contrast, in HCT 116 and HT29 human colon carcinoma cells, I3C inhibited growth and induced G1-phase cell-cycle arrest and apoptosis. Furthermore, I3C caused approximately a 2- to 4-fold increase in the cellular levels of p27KIP1 and p21CIP1 mRNA. These results suggest that I3C inhibits the growth of human colon carcinoma cells, at least in part, by inducing p27KIP1 and p21CIP1-mediated G1 cell-cycle arrest but dietary I3C promotes AOM-induced rat colon carcinogenesis by inhibiting the apoptosis of colon tumors. Therefore, the present study may provide further evidence for the ambivalent modulatory activity of I3C and this information may be useful when including I3C in cancer chemoprevention and/or extensive clinical therapy trials. PMID: 16211236 [PubMed - in process] These results suggest that I3C inhibits the growth of human colon carcinoma cells, at least in part, by inducing p27KIP1 and p21CIP1-mediated G1 cell-cycle arrest but dietary I3C promotes AOM-induced rat colon carcinogenesis by inhibiting the apoptosis of colon tumors.

24. Biochem Biophys Res Commun. 2005 Nov 25;337(3):1019-25. 3,3'-Diindolylmethane, a cruciferous vegetable derived synthetic anti-proliferative compound in thyroid disease. Tadi K , Chang Y , Ashok BT , Chen Y , Moscatello A , Schaefer SD , Schantz SP , Policastro AJ , Geliebter J , Tiwari RK . Department of Microbiology and Immunology, New York Medical College, Valhalla, NY, USA. Considerable epidemiological evidence exists to link thyroid disease with differing patterns of dietary consumption, in particular, cruciferous vegetables. We have been studying the anti-thyroid cancer (TCa) activity of indole-3-carbinol (I3C) found in cruciferous vegetables and its acid catalyzed dimer, 3,3'-diindolylmethane (DIM). There are no studies as yet to elucidate the effect of these compounds on the altered proliferative patterns in goiter or thyroid neoplasia. In this study, we tested the anti-proliferative effects of I3C and DIM on four different thyroid cancer cell lines representative of papillary (B-CPAP and 8505-C) and follicular carcinoma of the thyroid (CGTH-W-1 and ML-1), and primary human goiter cells. Cell survival and IC50 values for I3C and DIM were calculated by the XTT assay and cell cycle distribution analysis was done by flow cytometry. DIM was found to be a better anti-proliferative agent than I3C in both papillary and follicular TCa resulting in a greater cytotoxic effect at a concentration over three fold lower than predicted by the molar ratio of DIM and I3C. The anti-proliferative activity of DIM in follicular TCa was mediated by a G1 arrest followed by induction of apoptosis. DIM also inhibited the growth of primary goiter cells by 70% compared to untreated controls. Contrary to traditional belief that cruciferous vegetables are &quot;goitrogenic&quot;, DIM has anti-proliferative effects in glandular thyroid proliferative disease. Our preclinical studies provide a strong rationale for the clinical exploration of DIM as an adjuvant to surgery in thyroid proliferative disease. PMID: 16219298 [PubMed - in process] DIM was found to be a better anti-proliferative agent than I3C in both papillary and follicular TCa resulting in a greater cytotoxic effect at a concentration over three fold lower than predicted by the molar ratio of DIM and I3C.

28. “ We have found that sulforaphane…is a potent bacteriostatic agent against….strains of H. pylori irrespective of their resistance to conventional antibiotics….sulforaphane blocked benzo[a]pyrene-evoked fore-stomach tumors… this protection resulted from induction of phase II detoxication and antioxidant enzymes.” PNAS; May 2002, Vol 99, no.11

29. Dietary Intake of Sulforaphane-Rich Broccoli Sprouts Improves Gastritis in H.pylori-Infected Human Subjects Abstract #3442 Akinori Yanaka, University of Tsukuba, Japan. Presented at the American Association for Cancer Research Meeting, Baltimore, MD; November 2, 2005 Yanaka and collegues found that over 2 months a diet rich in SGS significantly reduced Helicobactor pylori infection among a group of 20 individuals (vs 20 w/o SGS in diet)…he concluded that a diet rich in sulforaphane glucosinolate may help protect against gastric cancer, and hypothesized that this is due to the activation of gastric mucosal antioxidant enzymes that can protect the cells from H.pylori-induced DNA damage.

30. Rats were fed SGS…had a significant decrease in oxidative stress in cardiovascular and kidney tissues and increase in GSH content…decreased oxidative stress correlated with better endothelial-dependent relaxation of the aorta and significantly lower blood pressure. We conclude that a diet containing phase 2 protein inducers may also reduce the risk of developing cardiovascular problems of hypertension and atherosclerosis PNAS, May 2004; vol 101, no.18

31. “ . . . SF [sulforaphane] …activates transcription of phase II genes, whose products provide chemically versatile, often catalytic, and prolonged “indirect” antioxidant protection. . . . Intensification of endogenous … phase II enzymes by SF treatment may be a useful strategy to prevent photooxidative stress-related retinal diseases such as age-related macular degeneration, retinitis pigmentosa, and photic maculopathy.” Talalay, P Gao, X; PNAS; July 2004, vol 101, no 28

32. This is the first study to provide direct evidence that broccoli sprouts can enhance the body’s detoxifying system to help prevent cancer. Although previous laboratory studies indicated this was true, this is the first time that a direct observation of this effect in humans was possible. (200 adults) The blinded, placebo-controlled study was conducted in Jiangsu Province near Shanghai, a rural area where the incidence of liver cancer is extremely high due to consumption of foods tainted with aflatoxin …an inverse association was observed for excretion of diithiocarabmates and aflatoxin-DNA adducts in individuals receiving broccoli sprout glucosinolates Cancer Epidemiology Biomarkers & Prevention , Nov. 2005

33. Data from: Fahey et al. (Mar. 17, 2005) advance e-publication Carcinogenesis Khachick et al. (1999) Antioxidant Food Supplements in Human Health Fahey & Stephenson (2002) J.Agric. Food Chem. Phase 2 Response Induction by a Variety of Phytochemicals Potency -- Amount Required for CD ( µM) SULFORAPHANE PINOSTROBIN ZEAXANTHIN QUERCETIN CURCUMIN β -CAROTENE α -CAROTENE LUTEIN LYCOPENE CHLOROPHYLLIN VITAMIN B-12 CHLOROPHYLL

34. Phase 2 Enzyme Induction Potency of Broccoli: Effect of Plant Age 3-day sprouts seeds Market-stage broccoli heads Harvest-ready seed Inducer Activity Million Units / gram Plant Age (Days) Glucoraphanin Concentration

35. SULFORAPHANE ANTIBIOTIC Helicobacter INDUCTION OF PHASE 2 RESPONSE CELL CYCLE ARREST & APOPTOSIS Indirect ANTIOXIDANT Retina, Oxygen Toxicity ANTI-INFLAMMATORY Hypertension, Aging TUMOR INHIBITION

36. Lungs and Sulforaphane

37. Cytokine reduction with Sulforaphane

39. Breast and Sulforaphane

42. Sulforaphane and Prostate

46. Sulforaphane and Skin

50. Sulforaphane and Neurological