Cumin Prevents 17β-Estradiol-Associated Breast Cancer in ACI Rats.
Cumin Prevents 17β-Estradiol-Associated Breast Cancer in ACI Rats.
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DOI：
10.3390/ijms22126194
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发表时间：
2021-06-08
影响因子：
5.6
通讯作者：
Gupta RC
中科院分区：
文献类型：
--
作者：
Aqil F;Jeyabalan J;Munagala R;Ahmad I;Schultz DJ;Gupta RC
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，我们报告了以孜然粉和干燥乙醇提取物的形式通过饮食给予孜然(Cumin)对E2介导的乳腺肿瘤形成的抑制作用。雌性ACI大鼠给予AIN-93M饲料、添加孜然粉(5%和7.5%，w/w)或干式孜然乙醇提取物(1%，w/w)的饲料，然后皮下植入E2硅胶(1.2 cm；9 mg)。无论是孜然粉还是孜然提取物，都显著延迟了可触及的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%，而孜然粉组和提取物组分别只有55%和45%的动物有明显的肿瘤。孜然粉组和孜然提取物组的肿瘤体积(660±122比138±49和75±46 mm~3)和肿瘤多样性(4.21±0.43比1.16±0.26和0.9±0.29个肿瘤/动物)也明显减少。孜然粉饮食干预剂量和时间依赖地抵消了E_2相关的垂体生长，降低了乳腺组织中循环催乳素水平和增殖细胞核抗原水平。从机制上讲，孜然粉饮食可显著逆转雌激素受体α、细胞色素P1A1和细胞色素P1B1的调控。此外，孜然粉饲料逆转了受E2处理高度调控的miRNAs(miR-182、miR-375、miR-127和miR-206)的表达水平。我们用GC/MS分析了提取物的组成，确定了伞花烃和孜然醛为主要成分，并进一步检测到没有明显或全身毒性的迹象。因此，孜然生物活性物质能够以安全有效的方式显著延缓和预防E2介导的乳腺肿瘤的发生，并值得继续努力开发这些临床可翻译的香料生物活性物质作为抗BC的化学预防和治疗药物。
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.
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通讯作者：
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4.7
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