James Graham Brown Cancer Center, University of Louisville, Louisville, KY 40202, USA.
Department of Medicine, University of Louisville, Louisville, KY 40202, USA.
Int J Mol Sci. 2021 Jun 8;22(12):6194. doi: 10.3390/ijms22126194.
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 (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%, /) or dried ethanolic cumin extract (1%, /), 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 mm) 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.
乳腺癌（BC）是欠发达国家女性癌症死亡的主要原因，也是美国女性癌症死亡的第二大原因。在这项研究中，我们报告了通过饮食（如孜然粉）给予 （孜然）抑制 E2 介导的乳腺肿瘤发生，以及干燥的乙醇提取物。将雌性 ACI 大鼠分为 AIN-93M 饮食组或补充孜然粉（5%和 7.5%，/）或干燥乙醇孜然提取物（1%，/）的饮食组，然后用皮下 E2 硅酮植入物（1.2 厘米；9 毫克）进行挑战。两种孜然粉和提取物都显著延迟了可触及乳腺肿瘤的首次出现。在研究结束时，对照组的肿瘤发生率为 96%，而孜然粉和提取物组分别只有 55%和 45%的动物有可触及的肿瘤。肿瘤体积（660 ± 122 与 138 ± 49 和 75 ± 46 mm）和肿瘤多发性（4.21 ± 0.43 与 1.16 ± 0.26 和 0.9 ± 0.29 个/动物）也分别观察到明显减少。孜然粉饮食干预剂量和时间依赖性地抵消了 E2 相关的垂体生长，并降低了循环催乳素水平和乳腺组织中的 PCNA 水平。从机制上讲，孜然粉饮食导致 E2 相关的 ERα、CYP1A1 和 CYP1B1 调节显著逆转。此外，孜然粉饮食还逆转了 miR-182、miR-375、miR-127 和 miR-206 等 miRNA 的表达水平，这些 miRNA 受 E2 处理的高度调节。我们通过 GC/MS 分析了提取物的组成，确定了伞形花内酯和枯茗醛为主要成分，并进一步检测到没有明显的全身或系统毒性迹象。因此，孜然生物活性可以以安全有效的方式显著延迟和预防 E2 介导的乳腺肿瘤发生，并值得继续努力开发这些具有临床转化潜力的香料生物活性物质作为乳腺癌的化学预防和治疗药物。
Zotero 插件
