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

Farrukh Aqil,David J Schultz,Iqbal Ahmad,Radha Munagala,Jeyaprakash Jeyabalan,Ramesh C Gupta

doi:10.3390/ijms22126194

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.

Highlights

IntroductionAbout 80% of all Breast cancer (BC) cases are estrogen receptor α (ERα)-positive [4] and ~50% of BC cases can be attributed to specific risk factors, including hormone exposure, gene mutations (e.g., BRCA1 and BRCA2), breast density, and obesity
We examined the associations of mammary tumorigenesis with circulating estradiol
To more completely delay tumor indices, including tumor latency, incidence, multiplicity andaddress tumorthe burden potential efficacy of cumin to modulate Breast cancer (BC) outcomes, we addressed a number of research in the E2- mediated August Copenhagen Irish (ACI) rat mammary tumorigenesis

Summary

Introduction

About 80% of all BC cases are estrogen receptor α (ERα)-positive [4] and ~50% of BC cases can be attributed to specific risk factors, including hormone exposure, gene mutations (e.g., BRCA1 and BRCA2), breast density, and obesity. The treatment for BC is usually multifaceted, including surgery, chemotherapy, radiation, and hormone therapy. These treatments burden patients with side effects that reduce therapy compliance and quality of life. In most patients where BC arises not from single gene mutations (or discrete combinations) [5,6], selective estrogen-receptor modulators (SERMs), e.g., tamoxifen and raloxifene, are approved for both the treatment and prevention of BC and decrease BC risk by about 35% [7]. With the rise in obesity in the US (and world-wide), and the associated increase in BC risk [10], it is imperative to develop simple and effective strategies to prevent BC

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