Cellular uptake of soy-derived phytoestrogens in vitro and in human whole blood

Epidemiological studies comparing typical Western and traditional Eastern lifestyles indicate that dietary intake of soyderived phytoestrogens, including genistein, daidzein, and equol, may have significant health protective effects on hormone-dependent cancers, osteoporosis and cardiovascular diseases. Phytoestrogens have been demonstrated to exert varying effects depending on tissue, endogenous hormone concentrations, and receptor types. Thus, a detailed understanding of the biodistribution and bioavailability of specific phytoestrogens is required in order to predict the subsequent biologic activities. In this study we aimed to investigate the cellular uptake of these soy-derived phytoestrogens in different cell types, including the mammary MCF-7/6 and MDAB-MB 231 cell lines, the ovarian Ishikawa Var-I cell lines and in murine adipocyte clusters. Furthermore, the biodistribution between serum and cell fraction was also investigated in human whole blood. Equol generally shows a higher cellular uptake when compared with genistein and daidzein. Therefore, equol may be more potent with respect to its relative bioactivity, which is corroborated by the observations of specific health effects associated with the equol-producer phenotype

Selective glucocorticoid receptor-activating adjuvant therapy in cancer treatments

Although adverse effects and glucocorticoid resistance cripple their chronic use, glucocorticoids form the mainstay therapy for acute and chronic inflammatory disorders, and play an important role in treatment protocols of both lymphoid malignancies and as adjuvant to stimulate therapy tolerability in various solid tumors. Glucocorticoid binding to their designate glucocorticoid receptor (GR), sets off a plethora of cell-specific events including therapeutically desirable effects, such as cell death, as well as undesirable effects, including chemotherapy resistance, systemic side effects and glucocorticoid resistance. In this context, selective GR agonists and modulators (SEGRAMs) with a more restricted GR activity profile have been developed, holding promise for further clinical development in anti-inflammatory and potentially in cancer therapies. Thus far, the research into the prospective benefits of selective GR modulators in cancer therapy limped behind. Our review discusses how selective GR agonists and modulators could improve the therapy regimens for lymphoid malignancies, prostate or breast cancer. We summarize our current knowledge and look forward to where the field should move to in the future. Altogether, our review clarifies novel therapeutic perspectives in cancer modulation via selective GR targeting