Genistein
From Wikipedia, the free encyclopedia
| Genistein | |
|---|---|
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| IUPAC name | 5,7-Dihydroxy-3-(4-hydroxyphenyl)chromen-4-one |
| Other names | 4',5,7-Trihydroxyisoflavone |
| Identifiers | |
| CAS number | [446-72-0] |
| PubChem | |
| SMILES | C1=CC(=CC=C1C2=COC3=CC(=CC(=C3C2=O)O)O)O |
| Properties | |
| Molecular formula | C15H10O5 |
| Molar mass | 270.24 g mol-1 |
| Except where noted otherwise, data are given for materials in their standard state (at 25 °C, 100 kPa) Infobox disclaimer and references |
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Genistein is one of several known isoflavones. Isoflavones, such as genistein and daidzein, are found in a number of plants, with soybeans and soy products like tofu and textured vegetable protein being the primary food source. Soy isoflavones are a group of compounds found in and isolated from the soybean. Besides functioning as antioxidants, many isoflavones have been shown to interact with animal and human estrogen receptors, causing effects in the body similar to those caused by the hormone estrogen. Soy isoflavones also produce non-hormonal effects.
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[edit] Biological effects
[edit] Antioxidant
Some isoflavones act as antioxidants to counteract damaging effects of free radicals in tissues. Genistein has a converse effect in this area compared to other isoflavones; It stimulates a step in nitrate synthesis, which is oxidation.[1]
[edit] Atherosclerosis
[edit] Cancer links
Some isoflavones have been found to have antiangiogenic effects (blocking formation of new blood vessels), and may block the uncontrolled cell growth associated with cancer, most likely by inhibiting the activity of substances in the body that regulate cell division and cell survival (growth factors). If Genistein has this effect, then it still has the net effect of promoting cancer in one study.[3]
Studies show that gastrointestinal cancer occurs less frequently among North Americans who do not learn to eat meat. North Americans who go to other continents without learning to eat vegetables show more digestive tract cancer than neighbours.[4] Timing of phytoestrogen use is important.[5] Genistein makes some cells more sensitive to radio-therapy.[6]
Though research is still ongoing, some recent studies have indicated that soy's phytoestrogens could be contributive factors in some forms of breast cancer, penile birth defects, and infantile leukemia. [7]Some studies have raised the concern that genistein might increase the risk of leukemia, because it inhibits the enzyme topoisomerase which results in double strand DNA breaks, which are, in turn, mutagenic. Some cancer patients whose chemotherapy drugs inhibited topoisomerase later developed leukemia. NCI researchers have completed animal studies on genistein with no adverse effects being seen.[8]Clinical trials with humans are in progress.
Regardless, soy's phytoestrogens, or isoflavones, have been definitely shown to depress thyroid function and to cause infertility in every animal species studied so far.[9] [10]
Genistein's chief method of activity is as a tyrosine kinase inhibitor. Tyrosine kinases are less widespread than their ser/thr counterparts but implicated in almost all cell growth and proliferation signal cascades. Genistein has been used to selectively target pre B-cells via conjugation with an antibody. This highly successful study in mice has promising benefits for future chemotherapy
[edit] Effects in males
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 proven genistein to induce apoptosis of testicular cells at certain levels, thus raising concerns about effects it could have on male fertility.[11]
[edit] Molecular function
Genistein influences several targets in living cells. One important function is the inhibition of several tyrosine kinases. Genistein also inhibits the mammalian hexose transporter GLUT1 and contraction of several types of smooth muscles. Genistein can bind to CFTR receptors. This binding causes the channel to become permanently open causing "free-flow" of chloride ions through the channel.
[edit] Sources
Concentrations of genistein in Pueraria mirifica (White Kawo Krua) are so close to zero that experimental estimates of error equalled concentration measured.[12]
[edit] References
- ^ "Genistein acutely stimulates nitric oxide synthesis in vascular endothelial cells by a cyclic adenosine 5'-monophosphate-dependent mechanism." . Endocrinology. PMID 15319357. “These findings demonstrated that genistein had direct nongenomic effects on eNOS activity in vascular endothelial cells, leading to eNOS activation and nitric oxide synthesis.”
- ^ "Phytochemical genistein in the regulation of vascular function: new insights." . Current Medicinal Chemistry. PMID 17979711. “However, genistein protects against pro-inflammatory factor-induced vascular endothelial barrier dysfunction and inhibits leukocyte-endothelium interaction, thereby modulating vascular inflammation, a major event in the pathogenesis of atherosclerosis.”
- ^ "Genistein enhances insulin-like growth factor signaling pathway in human breast cancer (MCF-7) cells." . The Journal of Clinical Endocrinology and Medicine. PMID 15126563. “These effects could be completely abolished by cotreatment of MCF-7 cells with estrogen antagonist ICI 182780 (1 microM) and tamoxifen (0.1 microM).”
- ^ "Nutrition and diet in the development of gastrointestinal cancer." . Current Oncology Reports. PMID 12667416. “...the capacity for diet to alter Helicobacter pylori infection should be explored.”
- ^ "Timing of dietary estrogenic exposures and breast cancer risk." . PMID 17261753. “Thus, dietary exposures during pregnancy and puberty may play an important role in determining later risk by inducing epigenetic changes that modify vulnerability to breast cancer.”
- ^ "Sensitization of the apoptotic effect of gamma-irradiation in genistein-pretreated CaSki cervical cancer cells." . Journal of microbiology and biotechnology. PMID 18388472. “The viability was decreased by co-treatment with genistein and irradiation compared with irradiation treatment alone.”
- ^ "Maternal exposure to genistein during pregnancy increases carcinogen-induced mammary tumorigenesis in female rat offspring" . PMID 10425307. “A high estrogenic environment in utero may increase subsequent breast cancer risk...increasing susceptibility to carcinogen-induced mammary tumorigenesis in rats exposed to genistein in utero.”
- ^ "Genistein stimulates growth of human breast cancer cells in a novel, postmenopausal animal model, with low plasma estradiol concentrations" . Carcinogenesis. PMID 16537557. “Results from this study suggest that consumption of products containing GEN may not be safe for postmenopausal women with estrogen-dependent breast cancer.”
- ^ The Myths of Vegetarianism, Westin A. Price Foundation
- ^ (a) K D R Setchell and others. Dietary estrogens - a probable cause of infertility and liver disease in captive cheetahs. Gastroenterology, 1987, 93: 225-233; (b) A S Leopold. Phytoestrogens: Adverse effects on reproduction in California Quail. Science, 1976, 191:98-100; (c) HM Drane and others. Oestrogenic activity of soya-bean products. Food Cosm Tech, 1980, 18: 425-427; (d) S Kimura and others. Development of malignant goiter by defatted soybean with iodine-free diet in rats. Gann, 1976, 67:763-765; (e) C Pelissero and others. Estrogenic effect of dietary soy bean meal on vitellogenesis in cultured Siberian Sturgeon Acipenser baeri. Gen Comp End 83:447-457; (f) Braden and others. The oestrogenic activity and metabolism of certain isoflavones in sheep. Australian J of Agric Res, 1967, 18:335-348.
- ^ Kumi-Diaka J, Rodriguez R, Goudaze G (1998). "Influence of genistein (4',5,7-trihydroxyisoflavone) on the growth and proliferation of testicular cell lines". Biol. Cell 90 (4): 349-54. PMID 9800352. “Genistein-induced apoptosis identifies genistein as a potential diagnostic and therapeutic tool in testicular pathophysiological research.”
- ^ Wichai CHERDSHEWASART and Suttijit SRIWATCHARAKUL (2007). "Major Isoflavonoid Contents of the 1-Year-Cultivated Phytoestrogen-Rich Herb, Pueraria mirifica" 71: 2531. Bioscience, Biotechnology, and Biochemistry. doi:. PMID 17928711.
