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.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA125152-04
Application #
7851052
Study Section
Chemo/Dietary Prevention Study Section (CDP)
Program Officer
Milner, John A
Project Start
2007-07-01
Project End
2012-05-31
Budget Start
2010-06-01
Budget End
2011-05-31
Support Year
4
Fiscal Year
2010
Total Cost
$281,200
Indirect Cost
Name
University of Louisville
Department
Pharmacology
Type
Schools of Medicine
DUNS #
057588857
City
Louisville
State
KY
Country
United States
Zip Code
40292
Aqil, Farrukh; Jeyabalan, Jeyaprakash; Munagala, Radha et al. (2017) Chemoprevention of Rat Mammary Carcinogenesis by Apiaceae Spices. Int J Mol Sci 18:
Aqil, Farrukh; Gupta, Ramesh C (2016) Controlled Delivery of Chemopreventive Agents by Polymeric Implants. Methods Mol Biol 1379:1-11
Aqil, Farrukh; Jeyabalan, Jeyaprakash; Munagala, Radha et al. (2016) Prevention of hormonal breast cancer by dietary jamun. Mol Nutr Food Res 60:1470-81
Munagala, Radha; Aqil, Farrukh; Jeyabalan, Jeyaprakash et al. (2016) Bovine milk-derived exosomes for drug delivery. Cancer Lett 371:48-61
Jeyabalan, Jeyaprakash; Aqil, Farrukh; Soper, Lisa et al. (2015) Potent Chemopreventive/Antioxidant Activity Detected in Common Spices of the Apiaceae Family. Nutr Cancer 67:1201-7
Bansal, Shyam S; Kausar, Hina; Vadhanam, Manicka V et al. (2014) Curcumin implants, not curcumin diet, inhibit estrogen-induced mammary carcinogenesis in ACI rats. Cancer Prev Res (Phila) 7:456-65
Jeyabalan, Jeyaprakash; Aqil, Farrukh; Munagala, Radha et al. (2014) Chemopreventive and therapeutic activity of dietary blueberry against estrogen-mediated breast cancer. J Agric Food Chem 62:3963-71
Aqil, Farrukh; Vadhanam, Manicka V; Jeyabalan, Jeyaprakash et al. (2014) Detection of anthocyanins/anthocyanidins in animal tissues. J Agric Food Chem 62:3912-8
Munagala, Radha; Aqil, Farrukh; Vadhanam, Manicka V et al. (2013) MicroRNA 'signature' during estrogen-mediated mammary carcinogenesis and its reversal by ellagic acid intervention. Cancer Lett 339:175-84
Bansal, Shyam S; Kausar, Hina; Vadhanam, Manicka V et al. (2012) Controlled systemic delivery by polymeric implants enhances tissue and plasma curcumin levels compared with oral administration. Eur J Pharm Biopharm 80:571-7

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