The Impact of Soy Isoflavones on MCF-7 and MDA-MB-231 Breast Cancer Cells Using a Global Metabolomic Approach

Abstract

Despite substantial research, the understanding of the chemopreventive mechanisms of soy isoflavones remains challenging. Promising tools, such as metabolomics, can provide now a deeper insight into their biochemical mechanisms. The purpose of this study was to offer a comprehensive assessment of the metabolic alterations induced by genistein, daidzein and a soy seed extract on estrogen responsive (MCF-7) and estrogen non-responsive breast cancer cells (MDA-MB-231), using a global metabolomic approach. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay showed that all test compounds induced a biphasic effect on MCF-7 cells and only a dose-dependent inhibitory effect on MDA-MB-231 cells. Proton nuclear magnetic resonance (1H-NMR) profiling of extracellular metabolites and gas chromatography-mass spectrometry (GC-MS) profiling of intracellular metabolites confirmed that all test compounds shared similar metabolic mechanisms. Exposing MCF-7 cells to stimulatory concentrations of isoflavones led to increased intracellular levels of 6-phosphogluconate and ribose 5-phosphate, suggesting a possible upregulation of the pentose phosphate pathway. After exposure to inhibitory doses of isoflavones, a significant decrease in glucose uptake was observed, especially for MCF-7 cells. In MDA-MB-231 cells, the glutamine uptake was significantly restricted, leading to alterations in protein biosynthesis. Understanding the metabolomic alterations of isoflavones represents a step forward in considering soy and soy derivates as functional foods in breast cancer chemoprevention.

Therapeutic Applications of Rose Hips from Different Rosa Species

“…They suggest that their content in isoflavone phytoestrogens may stimulate the growth of oestrogen-dependent cells like MCF-7 are [87]. So in conclusion, the therapeutic use of Rosa canina may be limited to glycolytic cancer and should be avoided in oestrogen-dependent tumours in order not to promote cancer growth.…”

Valuable Food Molecules with Potential Benefits for Human Health

“…In contrast, in estrogen-independent breast cancer cells, this twofold effect was not observed. In these cells, isoflavones have induced only antiproliferative effects, particularly after high dose exposure [155][156][157][158]. These observations have concluded that genistein can induce estrogenic and antiestrogenic effects (depending on the dose), but other cytotoxic mechanisms might be involved as well.…”

Daidzein derivative daid002 inhibits glioblastoma growth via disrupting the interaction between moesin and CD44

“…For acute toxicity experiments, ICR mice were divided into eight groups (10 mouse per group, half male and female) and daid002 was given intravenously (16,12,8,4, 2, 1, 0.5 mg/kg). LD50 was calculated by SPSS 22.0 via regression analysis.…”

“…Daidzein (daid) was found to inhibit the proliferation of breast cancer cell lines, including T-47D, MCF-7 and MDA-MB-231 cells with low toxicity [15,16]. Subtoxic doses of daid combined with TRAIL induced rapid apoptosis in glioma cells [17].…”