Abstract
Although soy consumption is associated with breast cancer prevention, the low bioavailability and the extensive metabolism of soy-active components limit their clinical application. Here, the impact of daidzein (D) and its metabolites on estrogen-dependent anti-apoptotic pathway has been evaluated in breast cancer cells. In estrogen receptor α-positive breast cancer cells treated with D and its metabolites, single or in mixture, ERα activation and Neuroglobin (NGB) levels, an anti-apoptotic estrogen/ERα-inducible protein, were evaluated. Moreover, the apoptotic cascade activation, as well as the cell number after stimulation was assessed in the absence/presence of paclitaxel to determine the compound effects on cell susceptibility to a chemotherapeutic agent. Among the metabolites, only D-4′-sulfate maintains the anti-estrogenic effect of D, reducing the NGB levels and rendering breast cancer cells more prone to the paclitaxel treatment, whereas other metabolites showed estrogen mimetic effects, or even estrogen independent effects. Intriguingly, the co-stimulation of D and gut metabolites strongly reduced D effects. The results highlight the important and complex influence of metabolic transformation on isoflavones physiological effects and demonstrate the need to take biotransformation into account when assessing the potential health benefits of consumption of soy isoflavones in cancer.
Highlights
Soy consumption is associated with breast cancer prevention, the low bioavailability and the extensive metabolism of soy-active components limit their clinical application
We investigated the potential interference of daidzein on this pathway and evaluated if its metabolites produced mainly from gut microbiota and from both liver and gut enzymes (D-4’-sulfate, D4S, D-7-sulfate, D7S, and D-4’,7-disulfate, DDS) mimic D
The results clearly indicate that daidzein (1–10 μM) and D4S (0.1–1 μM) reduced the basal level of NGB levels in MCF-7 cells
Summary
Soy consumption is associated with breast cancer prevention, the low bioavailability and the extensive metabolism of soy-active components limit their clinical application. The main dietary source of isoflavones in humans are soybean and soybean products, which contain mainly daidzein (7,40 -dihydroxyisoflavone, D) and genistein (7, 40 -dihydroxy-6-methoxyisoflavone), whose potential efficacy against breast cancer is well documented [7,8,9,10,11,12]. These data are promising for the use of these compounds as anticancer therapeutic agents, the therapeutic application of isoflavones is still limited, mainly due to their scarce bioavailability in human beings
Sign-in/Register to view highlights & summary 
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
