Oct. 22-25, 2012

Zhenjiang, China

Royal Jelly is Free from Estrogens and Does Not Promote Proliferation of Human Breast Cancer MCF-7 Cells in Mice

XIA Hai-Ou 1, ZHAO Yue 2, NIU Kai-jun 3, Hiroko Tani 4, Ken Hashimoto 4

(1.The School of Nursing, Fudan University, Shanghai 200032, China; 2. The School of Nursing, Tianjin Medical University, Tianjin 300070, China; 3. Department of Epidemiology, School of Public Health, Tianjin Medical University, Tianjin, China; 4 .Institute for Bee Products and Health Science, Yamada Apiculture Center, Inc., 194 Ichiba, Kagamino 708-0393, Japan)

【Background and Objective】Royal jelly (RJ), a secretion of honeybees (Apis mellifera), has been

consumed from ancient times as a food supplement in many countries. Its reported effectiveness includes improvement of stiff neck and sensitivity to cold in women. On the other hand, RJ has been considered to negatively affect breast cancer in some areas of China. In this study, we evaluated the effect of RJ on breast cancer cells in vitro and in vivo.

【Method】RJ and protease-treated RJ (pRJ) were analyzed by LC/MS for the presence of the three estrogens estrone, estradiol, and estriol. The rate of proliferation of estrogen-responsive human breast cancer MCF-7 cells stimulated with estradiol in the presence of RJ and pRJ (30, 100, 300 μg/mL) was determined by the AlamarBlue cell proliferation assay after 6 days of culture. In vivo, RJ and pRJ (1000 mg/kg p.o.) were administered daily to female SCID mice transplanted with MCF-7 cells and treated with estradiol (0.5 mg/kg/d i.p.) for 56 days as a model for the estrogen status in women. The effect on MCF-7 tumor growth was studied by measuring changes in the tumor volume. Tamoxifen, a medicinal substance for estrogen receptor positive breast cancer, was used as a positive control.

【Result and Discussion】 No estrogen was detected in the RJ or pRJ (limit of quantification : estron < 2 ppb; estradiol, estriol < 5 ppb). The proliferation rate of MCF-7 cells was not promoted by the combination of RJ or pRJ with estradiol. In mice administered estradiol for all of the test period, neither RJ nor pRJ significantly increased the MCF-7 tumor volume as compared to the controls. Tamoxifen showed significant inhibition of MCF-7 cell proliferation and tumor growth. In conclusion, these results show that RJ and pRJ are free of estrogens and do not promote the proliferation of breast cancer cells in vitro and in vivo. Thus, RJ is regarded as a highly safe food, and further study of its mechanisms of action and beneficial effects are ongoing.

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蜂王浆不含有雌性激素，并且不会促进小鼠体内MCF-7 乳腺癌细胞的增殖

XIA Hai-Ou 1, ZHAO Yue 2, NIU Kai-jun 3, Hiroko Tani 4, Ken Hashimoto 4

(1. 复旦大学护理学院，上海 200032，中国；2.天津医科大学护理学院，天津 300070，中国；3.中国天津医科大学流行病学学院、公共卫生学院，天津 300070，中国；4.日本蜂产品和保健科学研究所，山田养蜂业中心股份有限公司，194 Ichiba, Kagamino 708-0393，日本)

【背景和目的】蜂王浆，一种蜜蜂的分泌物（西方蜜蜂），在古代许多国家已经把它当做一种食物进行 食用。报告指出蜂王浆可以改善妇女落枕以及对女性体寒的体质有积极的效果。另一方面，在中国某些地 区，人们认为蜂胶对乳腺癌有消极的影响。在这个研究中，我们评估了蜂王浆在人体内和人体外对乳腺癌 细胞的作用。

【方法】LC / MS 分析了RJ 和蛋白酶处理RJ(pRJ)含有三个雌激素雌激素酮、雌二醇和雌三醇。对于雌 性激素敏感的人类乳腺癌MCF-7 细胞扩散的速率受RJ 和pRJ 里的雌二醇含量刺激(30,100,300 μg/mL) ,这个 结论由AlamarBlue 的细胞培养六天后的增殖试验得出。在活体内，移植了MCF-7 细胞的联合免疫缺陷鼠 每天管理RJ 和pRJ，并且用雌二醇治疗，根据女性体内雌性激素状态，以56 天作为一个周期。通过测量肿 瘤体积的变化研究MCF-7 肿瘤生长的影响。它莫西芬是对雌激素受体阳性乳腺癌的药用物质,被用来作为一个积极的控制。

【结果和讨论内容】在RJ 或者pRJ 中未发现雌性激素（限量：雌酮< 2 ppb; 雌二醇，雌三醇< 5 ppb）。将rj 或者prj 和雌二醇结合有利于提升MCF-7 细胞的繁殖速度。在老鼠身上的所有管理雌二醇测试期间, 无论使用RJ 或者pRJ，MCF-7 肿瘤体积对比于控制下也未显著增大。它莫西芬显著抑制细胞的增生和MCF-7 肿瘤的生长。总之，这些结果表明,RJ 和pRJ 不受雌激素影响，并且不促进体外和体内的乳腺癌细胞的增 殖。因此,RJ 是被视为极其安全的食物,它的作用机理和有益的影响将被持续进一步研究。