title: Chemoprevention of Rat Mammary Carcinogenesis by Apiaceae Spices.
abstract: Scientific evidence suggests that many herbs and spices have medicinal properties that alleviate symptoms or prevent disease. In this study, we examined the chemopreventive effects of the Apiaceae spices, anise, caraway, and celery seeds against 17β-estrogen (E2)-mediated mammary tumorigenesis in an ACI (August-Copenhagen Irish) rat model. Female ACI rats were given either control diet (AIN 93M) or diet supplemented with 7.5% (w/w) of anise, caraway, or celery seed powder. Two weeks later, one half of the animals in each group received subcutaneous silastic implants of E2. Diet intake and body weight were recorded weekly, and animals were euthanized after 3 and 12 weeks. E2-treatment showed significantly (2.1- and 3.4-fold) enhanced growth of pituitary gland at 3 and 12 weeks, respectively. All test spices significantly offset the pituitary growth by 12 weeks, except celery which was effective as early as three weeks. Immunohistochemical analysis for proliferative cell nuclear antigen (PCNA) in mammary tissues showed significant reduction in E2-mediated mammary cell proliferation. Test spices reduced the circulating levels of both E2 and prolactin at three weeks. This protection was more pronounced at 12 weeks, with celery eliciting the highest effect. RT-PCR and western blot analysis were performed to determine the potential molecular targets of the spices. Anise and caraway diets significantly offset estrogen-mediated overexpression of both cyclin D1 and estrogen receptor α (ERα). The effect of anise was modest. Likewise, expression of CYP1B1 and CYP1A1 was inhibited by all test spices. Based on short-term molecular markers, caraway was selected over other spices based on its enhanced effect on estrogen-associated pathway. Therefore, a tumor-end point study in ACI rats was conducted with dietary caraway. Tumor palpation from 12 weeks onwards revealed tumor latency of 29 days in caraway-treated animals compared with first tumor appearance at 92 days in control group. At the end of the study (25 weeks), the tumor incidence was 96% in the control group compared with only 70% in the caraway group. A significant reduction in tumor volume (661 ± 123 vs. 313 ± 81 mm³) and tumor multiplicity (4.2 ± 0.4 vs. 2.5 ± 0.5 tumors/animal) was also observed in the caraway group compared with the control group. Together, our data show dietary caraway can significantly delay and prevent the hormonal mammary tumorigenesis by modulating different cellular and molecular targets.
authors.affiliation: Department of Medicine, University of Louisville, Louisville, KY 40202, USA. f0aqil01@louisville.edu.
authors.forename: Farrukh
authors.initials: F
authors.lastname: Aqil
authors.affiliation: James Graham Brown Cancer Center, University of Louisville, Louisville, KY 40202, USA. j0jeya01@louisville.edu.
authors.forename: Jeyaprakash
authors.initials: J
authors.lastname: Jeyabalan
authors.affiliation: Department of Medicine, University of Louisville, Louisville, KY 40202, USA. r0muna01@louisville.edu.|James Graham Brown Cancer Center, University of Louisville, Louisville, KY 40202, USA. r0muna01@louisville.edu.
authors.forename: Radha
authors.initials: R
authors.lastname: Munagala
authors.affiliation: James Graham Brown Cancer Center, University of Louisville, Louisville, KY 40202, USA. srivani.ravoori@aacr.org.
authors.forename: Srivani
authors.initials: S
authors.lastname: Ravoori
authors.affiliation: James Graham Brown Cancer Center, University of Louisville, Louisville, KY 40202, USA. mvvadh01@louisville.edu.
authors.forename: Manicka V
authors.initials: MV
authors.lastname: Vadhanam
authors.affiliation: Department of Biology, University of Louisville, Louisville, KY 40202, USA. djschu02@louisville.edu.
authors.forename: David J
authors.initials: DJ
authors.lastname: Schultz
authors.affiliation: James Graham Brown Cancer Center, University of Louisville, Louisville, KY 40202, USA. rcgupta@louisville.edu.|Department of Pharmacology and Toxicology, University of Louisville, Louisville, KY 40202, USA. rcgupta@louisville.edu.
authors.forename: Ramesh C
authors.initials: RC
authors.lastname: Gupta
mesh_terms: D000818:Animals; D019661:Apiaceae / Q000737:chemistry*; D015415:Biomarkers; D001835:Body Weight; D049109:Cell Proliferation / Q000187:drug effects; D002471:Cell Transformation, Neoplastic / Q000187:drug effects*; D018890:Chemoprevention; D019587:Dietary Supplements; D004958:Estradiol / Q000009:adverse effects; D004967:Estrogens / Q000097:blood; D005260:Female; D008325:Mammary Neoplasms, Experimental / Q000097:blood / Q000473:pathology* / Q000517:prevention & control*; D011388:Prolactin / Q000097:blood; D051381:Rats; D017365:Spices; D047368:Tumor Burden
chemical_list: D015415:Biomarkers; D004967:Estrogens; D004958:Estradiol; D011388:Prolactin
keywords: ACI (August-Copenhagen Irish) rats; Apiaceae spices; breast cancer; chemoprevention; estradiol