Breast Cancer Chemoprevention Potential of Common Spices

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DESCRIPTION (provided by applicant): The female hormone, 1715-estradiol (E2) and its metabolites, particularly, 4-hydroxy-E2 (4E2), have been implicated in breast cancer. It is proposed that excessive estrogen exposure causes cell proliferation, and oxidative DNA damage, which may lead to gene mutations and ultimately breast cancer. It has become increasingly clear that the problem of breast cancer mortality cannot be solved by treatment alone. Therefore, attention has rightfully turned to the detection of early markers of exposure and disease prevention. Unlike the current trend, this application focuses on common spices belonging to one plant family for their potential against estrogen-mediated breast cancer. We hypothesize that phytochemicals present in common spices belonging to the Apiaceae family (anise, caraway, coriander, cumin, dill, and fennel) will favorably alter estrogen metabolism, oxidative DNA damage and cell proliferation, and ultimately diminish the mammary tumorigenesis. Results obtained from extracts of all the six spices have shown drastic reduction of estrogen-mediated oxidative DNA damage by inhibiting P450 activity and/or scavenging hydroxy radicals, as well as antiproliferative activity in vivo, supporting our working hypothesis. Our major objectives are to identify efficacious spices based on their modes of action to inhibit estrogen-mediated mammary tumorigenesis, and to correlate early markers with tumor indices. Specifically, i) determine potential of the spices in short-term in vivo assays to favorably modulate estrogen metabolism, oxidative DNA adduction, and cell proliferation; ii) determine efficacy of test spices to inhibit estrogen-mediated mammary tumorigenesis, and correlate modulation of early markers with tumor indices; and iii) determine potential of extracts of two selected spices against estrogen-mediated mammary cancer. Data resulting from this project will identify spices with the potential to inhibit breast cancer, and establish an association of early biomarkers with tumor indices. Efficacious extracts will in future be fractionated and active subfractions and purified component(s) will be tested for their efficacy against estrogen carcinogenicity and their effects on early biomarkers. Thus, the early biomarkers may identify women who may be at the higher risk of developing breast cancer much before the onset of pathologically detectable lesions, and prevent the disease by intervention with common house-hold spices.