Hyperplasia was characterized by thickened and multi-layered mammary ducts and cells with a large nucleus. of natural killer (NK) HPGDS inhibitor 2 cellsin vitro, dietary feeding of BITC failed to augment NK cell lytic activity in anex vivoassay. The present study demonstrating efficacy of BITC against mammary cancer in an animal model provides impetus to determine its activity in a clinical setting. Keywords:Benzyl isothiocyanate, Breast Cancer, Chemoprevention == Introduction == Breast cancer remains a leading cause of cancer related deaths in women despite significant advances in screening techniques, allowing for early detection of the disease, as well as continuous evolution of molecularly targeted therapies (1-4). The known risk factors for breast cancer include family history, Li-Fraumeni syndrome, atypical hyperplasia of the breast, late age at first full-term pregnancy, early menarche, and late menopause (5-7). Because some of these risk factors are not modifiable, novel strategies for prevention of breast cancer are highly desirable. Some success in prevention of mammary carcinogenesis has been achieved using selective estrogen-receptor modulators such as tamoxifen, but this strategy is ineffective against estrogen receptor negative breast cancers (8,9). In addition, selective estrogen-receptor modulators suffer from severe side effects including increased risk of uterine cancer, thromboembolism, cataracts, and perimenopausal symptoms (8,9). Accordingly, novel agents that are relatively safe but which could prevent onset and/or progression of breast cancer irrespective of the hormone receptor status are attractive. Natural products have received increased attention in recent years for the discovery of novel cancer chemopreventive and/or cancer therapeutic agents (10). Benefit of a diet rich in cruciferous vegetables as a modifier of the breast cancer risk is recognized by population-based, observational studies. For example, a case-control study involving >300 breast cancer cases and controls (matched by age, menopausal status, etc.) documented an inverse correlation between urinary levels of isothiocyanates (ITCs) as a biological measure of cruciferous vegetable intake and the risk of breast cancer (11). Consumption of cruciferous Rabbit Polyclonal to FGF23 vegetables was inversely associated with the risk of mammary cancer in premenopausal women in another population based case-control study (12). Anti-carcinogenic effect of cruciferous vegetables is attributed to ITCs, which are generated upon hydrolysis of corresponding glucosinolates through catalytic mediation of myrosinase (13,14). Benzyl isothiocyanate (BITC) is one such compound that has attracted increasing attention because of its ability to inhibit chemically-induced cancer in animal models (13,14). For example, BITC is a HPGDS inhibitor 2 potent inhibitor of mouse lung carcinogenesis induced by polycyclic hydrocarbons and hepatocarcinogenesis in rats induced by diethylnitrosamine (15,16). Dietary administration ofN-acetylcysteine conjugate of BITC inhibited benzo[a]pyrene-induced HPGDS inhibitor 2 lung tumorigenesis in A/J mice (17). Recent studies from our laboratory have shown that BITC inhibits viability of cultured human breast cancer cells by causing apoptosis (18). On the other hand, a spontaneously immortalized non-tumorigenic human mammary epithelial cell line (MCF-10A) is markedly more resistant to BITC-mediated growth inhibition HPGDS inhibitor 2 and apoptosis induction compared with breast cancer cells (18). We also showed that the proapoptotic effect of BITC against human breast cancer cells is triggered by generation of reactive oxygen species due to inhibition of mitochondrial respiratory chain (18,19). Despite compelling epidemiological and cellular evidence suggesting anti-cancer effect of BITC (11,12,18,19), studies on itsin vivoefficacy against breast cancer are lacking. Here, we show that dietary administration of BITC inhibits incidence and/or burden of mammary hyperplasia and carcinoma in female MMTV-neumice without causing any side effects. == Materials and Methods == == Reagents == BITC (purity ~98%) was purchased from LKT laboratories. Cell culture media, antibiotic mixture, and fetal.