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Introduction
Royal jelly (RJ) is a thick and milky liquid secreted by hypopharyngeal, and mandibular glands of young worker bees (Apismellifera L.), and is used to feed the larvae (1). RJ exhibits a wide variety of functional properties, and has been widely used in cosmetics, healthy foods and commercial medical products in numerous countries. Additionally, RJ possesses various properties, including antimicrobial (2), anti-inflammatory (3,4), hepatoprotective (5), antisarcopenia (6), insulin-like action (7) and antihypercholesterolemic (8) properties. In the recent decades, there have been an increasing number of studies investigating the effects of RJ.
Regarding breast cancer, RJ has been reported to be able to inhibit the growth-promoting effect of bisphenol A, which is an estrogen that enhances the proliferation of MCF-7 mammary cancer cells (9). RJP30, a substance obtained from RJ crude protein, which was extracted by precipitation with 30% ammonium sulfate, was demonstrated to be cytotoxic for HeLa human cervicouterine carcinoma cells, and diminish cell density to 50% of the original carcinoma cell after 7 days of treatment (10). RJ exhibited no significant effects on the formation of metastases in spontaneous mammary carcinoma of CBA mice when it was given intraperitoneally or subcutaneously (11). However, when RJ and tumor cells were injected synchronously into mice, RJ was able to inhibit the formation of metastases in the lung (11). The therapeutic properties of RJ have been examined in various cells, including MCF-7 (mouse macrophages), spontaneous mammary carcinoma cells and methylcholanthrene-induced fibrosarcoma CBA mouse cells (9,11,12).
RJ exhibits estrogenic activity. It was identified that RJ stimulated the expression of endogenous estrogen-responsive genes [presenilin 2 and vascular endothelial growth factor (VEGF)] by activating estrogen receptors in MCF-7 cells, and RJ could restore the expression of VEGF in uterus of rats that received bilateral ovariectomy (13). Experimental results demonstrated that four compounds from RJ can improve the transcription of a reporter gene, which contained an estrogen-responsive element, and subcutaneously injecting immature rats with those compounds for 23 days induced mild hypertrophy in the luminal epithelium of the rat uterus (14). With evidence that it was an etiological cause of breast cancer, estrogen attracted numerous studies on its association with breast carcinogenesis (15). Samavat and Kurzer (16) evaluated the roles and metabolites of circulating, and urinary estrogens in...