Traditional cytotoxic chemotherapeutic approaches have many adverse effects on patients with malignancies. Cancer chemoprevention is to use non-cytotoxicdrugs or natural products to prevent the occurrence or proliferation of cancer (1). Sulforaphane is a cancer chemopreventive agent discovered by Dr. Paul Talalay and his team at the Johns Hopkins University School of Medicine in 1992.They revealed three-day-old broccoli sprouts contained 20 to 50 times sulforaphane than mature broccoli heads in 1997. Sulforaphane belongs to a general classof natural products that contain an isothiocyanate moiety. Isothiocyanaates can be found in other cruciferous vegetables such as cauliflower, cabbage, kale and turnips too (2,3,4,5). Sulforaphane, also known as 4-methylsulfinylbutyl isothiocyanates and (-)-1-isothiocyanato-4-(R)-(methylsulfinyl) butane, has many interesting properties such as antimicrobial, antioxidant and antitumor activities. It is reported that sulforaphane inhibits extracellular, intracellular, and antibiotic-resistant strains of Helicobacterpylori (6). Synthetic sulforaphane (a racemic mixture) has been shown to be an effective agent in chemoprevention of chemically induced mammary tumors in rats (7).Sulforaphane exerts its cancer chemopreventive property via the activation of detoxifying enzymes and induction of apoptosis.

Phase I enzymes activate many carcinogens to highly reactive electrophilic metabolites capable of damaging DNA. Phase II enzymes convert these reactiveelectrophiles to less toxic and more easily excretable products (8). Sulforaphane is a very potent inducer of Phase 2 detoxication enzymes such as glutathione S-transferase (GST) and quinone reductase (QR) 9-14. The induction of Phase II enzymes is mediated by a mitogen-activated protein kinase pathway (13,14).Sulforaphane increased quinone reductase activity at low concentration of 0.5 –1 μM and raised glutathione level in a dose-dependent manner in human lym-phoblastoid cells (1). In human prostate cell lines sulforaphane was found to induce QR, GSTand g-glutamylcysteine synthetase accompanied by an increase ofGSH synthesis (15). In human epithelial cell line MCF-10F sulforaphane was found to inhibit benzo[a]pyrene-DNAand 1,6-dinitropyrene-DNAadducts formation. The inhibition of adducts formation was correlated with increase in QR and GSTprotein expression (12).Sulforaphane is a strong Phase I enzymes inhibitor 16. It inhibits the phase I cytochrome P450 isoenzymes 2E1 and 1A2 which have been associated with theactivation of carcinogens (17,18).Myzak MC and colleagues discovered sulforaphane also acted as an inhibitor of histone deacetylase (HDAC) in HCT116 human colorectal cancer cells. Theysuggest sulforaphane may be effective as a tumor-suppressing agent and as a chemotherapeutic agent (19). The anticarcinogenic effect of sulforaphane has beenattributed also to its ability to induce multidrug resistance-associated protein (2) in primary rat and human heptocytes (20).In addition to the activation of detoxifying enzymes, induction of apoptosis is also involved in the sulforaphane-associated cancer chemoprevention. Sulforaphane induces apoptosis in various types of cancer cell lines. At 2.5 – 10 μM concentration sulforaphane is a cell growth modulator. The IC50 for sul-foraphane in lymphoblastoid cells and human breast cancer MCF-7 cells was 3.9 μM and 13.7 μM, respectively( 1,21). Sulforaphane (10-30 μM)-induced HT29human colon cancer cell cycle arrest, followed by cell death, was correlated with an increased expression of cyclins Aand B1, increased expression of the proapoptotic protein bax, the release of cytochrome c from the mitochondria to the cytosol, and the proteolytic cleavage of poly (ADP-ribose) polymerase (7,22,23).Incubations human pancreatic cancer cells at higher sulforaphane doses (>10 micromol/L) resulted in cleavage of caspase-3 in the G1 subpopulation (24). Many sulforaphane analogs have been previously isolated from plants, but their enzyme inducing activity was less potent than that of sulforaphane (13). Thenaturally occurring sulforaphane is optically active with an R(-) configuration.