Cumin Prevents 17β-Estradiol-Associated Breast Cancer in ACI Rats

Abstract

Breast cancer (BC) is a leading cause of cancer deaths in women in less developed countries and the second leading cause of cancer death in women in the U.S. In this study, we report the inhibition of E2-mediated mammary tumorigenesis by Cuminum cyminum (cumin) administered via the diet as cumin powder, as well as dried ethanolic extract. Groups of female ACI rats were given either an AIN-93M diet or a diet supplemented with cumin powder (5% and 7.5%, w/w) or dried ethanolic cumin extract (1%, w/w), and then challenged with subcutaneous E2 silastic implants (1.2 cm; 9 mg). The first appearance of a palpable mammary tumor was significantly delayed by both the cumin powder and extract. At the end of the study, the tumor incidence was 96% in the control group, whereas only 55% and 45% animals had palpable tumors in the cumin powder and extract groups, respectively. Significant reductions in tumor volume (660 ± 122 vs. 138 ± 49 and 75 ± 46 mm3) and tumor multiplicity (4.21 ± 0.43 vs. 1.16 ± 0.26 and 0.9 ± 0.29 tumors/animal) were also observed by the cumin powder and cumin extract groups, respectively. The cumin powder diet intervention dose- and time-dependently offset E2-related pituitary growth, and reduced the levels of circulating prolactin and the levels of PCNA in the mammary tissues. Mechanistically, the cumin powder diet resulted in a significant reversal of E2-associated modulation in ERα, CYP1A1 and CYP1B1. Further, the cumin powder diet reversed the expression levels of miRNAs (miR-182, miR-375, miR-127 and miR-206) that were highly modulated by E2 treatment. We analyzed the composition of the extract by GC/MS and established cymene and cuminaldehyde as major components, and further detected no signs of gross or systemic toxicity. Thus, cumin bioactives can significantly delay and prevent E2-mediated mammary tumorigenesis in a safe and effective manner, and warrant continued efforts to develop these clinically translatable spice bioactives as chemopreventives and therapeutics against BC.

A Comprehensive Review on the Importance of MiRNA-206 in the Animal Model and Human Diseases

“…Furthermore, the major phytochemical constituents of cumin are cuminaldehyde and cymene, which have been proven to stimulate the activities of cytochrome p450s, aryl hydroxylase, and N-demethylase in rats [ 114 ]. The cumin powder diet reversed the expression levels of miR-206 that were highly modulated by 17ß-estradiol (E2) treatment in August Copenhagen Irish (ACI) rats with breast cancer [ 115 ].…”

Health Benefits of Cumin in Foods: A Review

“…The excretion of fecal bile acids and neutral sterols benefi cially increased, and cumin showed nourish the colon and reduced the activity of mucinase enzymes and β-glucuronidase [56]. β-glucuronidase rise hydrolysis of glucuronide compound and liberate toxin whereas the rise in mucinase activity may enhance the hydrolysis of the colon's protecting mucins [57]. Histopathology analysis revealed that decreased infi ltration into the submucosa, lesser papillae, and fewer changes in the cytoplasma cell in the cumin treated colon [46].…”