Abstract 1879: Chemoprevention of rat mammary carcinogenesis by Apiaceae spices: Potential mechanisms

Proceedings: AACR 101st Annual Meeting 2010‐‐ Apr 17‐21, 2010; Washington, DC Spices have been used for generations in cuisines, as well as in the treatment of various ailments as part of folklore medicine. Scientific evidence suggests that many herbs and spices have medicinal properties that alleviate symptoms or prevent disease. We have previously demonstrated that certain Apiaceae spices (fennel, cumin and ajowan) are protective against oxidative DNA adducts and estrogen-induced changes in the ACI rat mammary tumorigenesis model. Here we report on the chemopreventive potential of other Apiaceae spices with presumable distinct phytochemical profiles, namely, anise, caraway and celery seeds and their possible mechanisms, along with the previously studied spices. Groups of female ACI rats were given either control (AIN 93M) diet or diet supplemented with 7.5% (w/w) anise, caraway and celery seeds. Two weeks later, one half of the animals in each groups were treated with subcutaneous silastic implants of 17s-estradiol (1.2 cm; 9 mg). Rats received water and diet ad libitum. Diet intake and body weight were recorded weekly and animals were euthanized after 3 and 12 weeks. No significant difference was found in the diet intake and body weight gain suggesting that test spices were well tolerated at given doses. Estrogen treatment showed significantly (2.1 and 3.4 fold) enhanced growth of pituitary gland at 3 and 12 weeks, respectively. However all test spices significantly offset the pituitary growth by 12 weeks, except celery which was effective as early as 3 weeks. All test spices also significantly reduced the plasma prolactin level by 3 weeks, and this protection was more pronounced by 3 months, with celery eliciting the highest protection. Immunohistochemical analysis of PCNA in mammary tissues from three weeks studies has shown significant reduction in estrogen-mediated mammary cell proliferation by fennel, ajowan and cumin, analyzed thus far. To determine potential molecular targets of the spices, in the genomic and non-genomic pathways of estrogen-mediated mammary tumorigenesis, we analyzed mammary tissues for selected proteins by Western blot analysis. Diets supplemented with fennel, ajowan, caraway and cumin significantly offset estrogen-mediated overexpression of both cyclin D1 and ERα. Likewise the expression of CYP1B1 by Western analysis and CYP1A1 by RT-PCR were also found to be inhibited by fennel, ajowan and cumin. These data suggest that Apiaceae spices offset estrogen-mediated increases in i) mammary cell proliferation; ii) ERα; iii) cyclin D1; and iv) CYP1A1 and CYP1B1. Noteworthy is the reduction of circulating prolactin levels by the spices, which is one of the key factors in mammary tumorigenesis in this model. (Supported from the USPSH grant CA-125152 and Agnes Brown Duggan Endowment). Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1879.