Chemoprevention of Rat Mammary Carcinogenesis by Apiaceae Spices.
Chemoprevention of Rat Mammary Carcinogenesis by Apiaceae Spices.
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DOI：
10.3390/ijms18020425
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发表时间：
2017-02-16
影响因子：
5.6
通讯作者：
Gupta RC
中科院分区：
文献类型：
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作者：
Aqil F;Jeyabalan J;Munagala R;Ravoori S;Vadhanam MV;Schultz DJ;Gupta RC
科学证据表明，许多草药和香料具有缓解症状或预防疾病的药用特性。在这项研究中，我们在 ACI（爱尔兰八月哥本哈根）大鼠模型中检查了伞形科香料、茴香、香菜和芹菜籽对 17β-雌激素 (E2) 介导的乳腺肿瘤发生的化学预防作用。雌性 ACI 大鼠给予对照饮食 (AIN 93M) 或补充有 7.5% (w/w) 茴香、香菜或芹菜籽粉的饮食。两周后，每组中有一半的动物接受了 E2 的皮下硅橡胶植入物。每周记录饮食摄入量和体重，并在3周和12周后对动物实施安乐死。 E2 治疗显示，第 3 周和第 12 周时垂体生长分别显着增强（2.1 倍和 3.4 倍）。所有测试香料都在 12 周内显着抵消了垂体的生长，但芹菜除外，它最早在三周内就有效。乳腺组织中增殖细胞核抗原 (PCNA) 的免疫组织化学分析显示 E2 介导的乳腺细胞增殖显着减少。三周后，测试香料降低了 E2 和催乳素的循环水平。这种保护作用在第 12 周时更加明显，其中芹菜的效果最高。进行 RT-PCR 和蛋白质印迹分析以确定香料的潜在分子靶点。茴香和香菜饮食可显着抵消雌激素介导的细胞周期蛋白 D1 和雌激素受体 α (ERα) 的过度表达。茴香的作用不大。同样，CYP1B1 和 CYP1A1 的表达被所有测试香料抑制。基于短期分子标记，香菜比其他香料被选择是因为它对雌激素相关途径的增强作用。因此，在 ACI 大鼠中进行了一项食用香菜的肿瘤终点研究。 12周后的肿瘤触诊显示，香菜治疗组动物的肿瘤潜伏期为29天，而对照组的首次肿瘤出现时间为92天。研究结束时（25 周），对照组的肿瘤发生率为 96%，而葛缕子组的肿瘤发生率为 70%。与对照组相比，香菜组的肿瘤体积（661 ± 123 vs. 313 ± 81 mm3）和肿瘤多样性（4.2 ± 0.4 vs. 2.5 ± 0.5 个肿瘤/动物）也显着减少。总之，我们的数据表明，膳食香菜可以通过调节不同的细胞和分子靶点来显着延迟和预防激素乳腺肿瘤的发生。
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.