Genistein is a phytoestrogen and belongs to the category of isoflavones. Genistein was first isolated in 1899 from the dyer's broom, Genista tinctoria; hence, the chemical name derived from the generic name. The compound nucleus was established in 1926, when it was found to be identical with prunetol. It was chemically synthesized in 1928.
Most of the isoflavones in plants are present in a glycosylated form. The unglycosylated aglycones can be obtained through various means such as treatment with the enzyme β-glucosidase, acid treatment of soybeans followed by solvent extraction, or by chemical synthesis. Acid treatment is a harsh method as concentrated inorganic acids are used. Both enzyme treatment and chemical synthesis are costly. A more economical process consisting of fermentation for in situ production of β-glucosidase to isolate genistein has been recently investigated.
Isoflavones genistein and daidzein bind to and transactivate all three PPAR isoforms, α, δ, and γ. For example, membrane-bound PPARγ-binding assay showed that genistein can directly interact with the PPARγ ligand binding domain and has a measurable Ki of 5.7 mM. Gene reporter assays showed that genistein at concentrations between 1 and 100 uM activated PPARs in a dose dependent way in KS483 mesenchymal progenitor cells, breast cancer MCF-7 cells, T47D cells and MDA-MD-231 cells, murine macrophage-like RAW 264.7 cells, endothelial cells and in Hela cells. Several studies have shown that both ERs and PPARs influenced each other and therefore induce differential effects in a dose-dependent way. The final biological effects of genistein are determined by the balance among these pleiotrophic actions.
Due to its structure similarity to 17β-estradiol (estrogen), genistein can compete with it and bind to estrogen receptors. However, genistein shows much higher affinity toward estrogen receptor β than toward estrogen receptor α.
Data from in vitro and in vivo research confirms that genistein can increase rate of growth of some ER expressing breast cancers. Genistein was found to increase the rate of proliferation of estrogen-dependent breast cancer when not cotreated with an estrogen antagonist. It was also found to decrease efficiency of tamoxifen and letrozole - drugs commonly used in breast cancer therapy. Genistein was found to inhibit immune response towards cancer cells allowing their survival.
Isoflavones can act like estrogen, stimulating development and maintenance of female characteristics, or they can block cells from using cousins of estrogen. In vitro studies have shown genistein to induce apoptosis of testicular cells at certain levels, thus raising concerns about effects it could have on male fertility; however, a recent study found that isoflavones had "no observable effect on endocrine measurements, testicular volume or semen parameters over the study period." in healthy males given isoflavone supplements daily over a 2-month period.
Genistein was, among other flavonoids, found to be a strong topoisomerase inhibitor, similarly to some chemotherapeutic anticancer drugs ex. etoposide and doxorubicin. In high doses it was found to be strongly toxic to normal cells. This effect may be responsible for both anticarcinogenic and carcinogenic potential of the substance. It was found to deteriorate DNA of cultured blood stem cells, what may lead to leukemia. Genistein among other flavonoids is suspected to increase risk of infant leukemia.
Genistein decreases pathological accumulation of glycosaminoglycans in Sanfilippo syndrome. In vitro animal studies and clinical experiments suggest that the symptoms of the disease may be alleviated by adequate dose of genistein. Genistein was found to also possess toxic properties toward brain cells. Among many pathways stimulated by genistein, autophagy may explain the observed efficiency of the substance as autophagy is significantly impaired in the disease.
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