Abstract 5443: Prevention of breast cancer by spices: Involvement of miRNA and other molecular targets

Proceedings: AACR 103rd Annual Meeting 2012‐‐ Mar 31‐Apr 4, 2012; Chicago, IL We have previously demonstrated the chemoprotective effects of dietary Apiaceae spices against estrogen induced mammary tumorigenesis in ACI rats by inhibiting cell proliferation and few cellular and molecular markers as early as three weeks of estrogen administration. Here we report inhibition of 17s-estradiol-mediated mammary carcinogenicity by fennel, cumin and caraway and potential mechanisms. Groups of female ACI rats were given either AIN-93M diet or diet supplemented with fennel, cumin and caraway (7.5% each, w/w) and then treated with subcutaneous 17s-estradiol silastic implants (1.2 cm; 9 mg). Four additional groups were maintained on control or experimental diets. Rats received diet and water ad libitum. Animals were euthanized when estrogen-treated group on control diet reached over 90% tumor incidence. Tumor palpation from 12 wks revealed first tumor incidence by 92 days in control group that was significantly delayed by 22, 37 and 29 days by fennel, cumin and caraway, respectively. At the end of the study (26 wks), the tumor incidence was found to be 96% in control group whereas only 83%, 55% and 90% animals had tumors in fennel, cumin and caraway groups, respectively. Significant reduction in tumor volume (661±123 vs 196±64, 138±50 and 313±81 mm3) and tumor multiplicity (4.2±0.4 vs 2.2±0.4, 1.1±0.3 and 2.5±0.5 tumors/animal) was also observed by fennel, cumin and caraway, respectively compared to control. All experimental diets significantly offset estrogen-related growth of pituitary prolactinomas, the plasma prolactin levels, and the cell proliferation marker, PCNA in the mammary tissues. The spice intervention had no significant effects on any of these markers in the absence of estrogen treatment. Mechanistically, all the experimental diets resulted in significant downregulation of estrogen-associated increase in the expression of the ERα and cyclin D1. We have recently reported ‘miRNA signature’ associated with estrogen treatment in the ACI rat model. Of the four candidate miRNAs, miR-182 and miR-375 which were overexpressed by 4- and 7-fold and miR-127 and miR-206 were downregulated by 17- and 35-fold, respectively with estrogen treatment. These miRNAs were significantly modulated favorably by dietary cumin analyzed thus far; molecules downstream of these miRNAs remain to be explored. Together, our data show that apiaceae spices can significantly delay and prevent estrogen-mediated mammary tumorigenesis, with maximal protective effects observed with cumin, by modulating different cellular and molecular targets, including key dysregulated miRNAs. (Supported by CA-125152 and Agnes Brown Duggan Endowment). Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5443. doi:1538-7445.AM2012-5443