Genistein

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ImageFile = Genistein.svg
ImageSize = 200px
IUPACName = 5,7-Dihydroxy-3-(4-hydroxyphenyl)chromen-4-one
OtherNames = 4',5,7-Trihydroxyisoflavone
Section1 = Chembox Identifiers
CASNo = 446-72-0
PubChem = 5280961
SMILES = C1=CC(=CC=C1C2=COC3=CC(=CC(=C3C2=O)O)O)O
Section2 = Chembox Properties
C=15 | H=10 | O=5
MolarMass = 270.241 g/mol
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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.

Biological effects

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.cite journal
author = Liu D, Homan LL, Dillon JS
title = Genistein acutely stimulates nitric oxide synthesis in vascular endothelial cells by a cyclic adenosine 5'-monophosphate-dependent mechanism
quote = These findings demonstrated that genistein had direct nongenomic effects on eNOS activity in vascular endothelial cells, leading to eNOS activation and nitric oxide synthesis.
journal = Endocrinology
volume = 145
issue = 12
pages = 5532–9
year = 2004
month = December
pmid = 15319357
doi = 10.1210/en.2004-0102
url = ]

Atherosclerosis

cite journal
author = Si H, Liu D
title = Phytochemical genistein in the regulation of vascular function: new insights
quote = 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.
journal = Curr. Med. Chem.
volume = 14
issue = 24
pages = 2581–9
year = 2007
pmid = 17979711
doi =
url = http://www.bentham-direct.org/pages/content.php?CMC/2007/00000014/00000024/0007C.SGM
issn = ]

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.cite journal
author = Chen WF, Wong MS
title = Genistein enhances insulin-like growth factor signaling pathway in human breast cancer (MCF-7) cells
quote = These effects could be completely abolished by cotreatment of MCF-7 cells with estrogen antagonist ICI 182780 (1 microM) and tamoxifen (0.1 microM).
journal = J. Clin. Endocrinol. Metab.
volume = 89
issue = 5
pages = 2351–9
year = 2004
month = May
pmid = 15126563
doi =
url = http://jcem.endojournals.org/cgi/pmidlookup?view=long&pmid=15126563
issn = ]

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.cite journal
author = Thomson CA, LeWinn K, Newton TR, Alberts DS, Martinez ME
title = Nutrition and diet in the development of gastrointestinal cancer
quote = ...the capacity for diet to alter Helicobacter pylori infection should be explored.
pmid = 12667416
journal = Curr Oncol Rep
volume = 5
issue = 3
pages = 192–202
year = 2003
month = May
doi =
url =
issn = ]

Timing of phytoestrogen use is important.cite journal
author = De Assis S, Hilakivi-Clarke L
title = Timing of dietary estrogenic exposures and breast cancer risk
quote = 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.
journal = Ann. N. Y. Acad. Sci.
volume = 1089
issue =
pages = 14–35
year = 2006
month = November
pmid = 17261753
doi = 10.1196/annals.1386.039
url = ]

Genistein makes some cells more sensitive to radio-therapy.cite journal
author = De Assis S, Hilakivi-Clarke L
title = Timing of dietary estrogenic exposures and breast cancer risk
quote = The viability was decreased by co-treatment with genistein and irradiation compared with irradiation treatment alone.
journal = Ann. N. Y. Acad. Sci.
volume = 1089
issue =
pages = 14–35
year = 2006
month = November
pmid = 17261753
doi = 10.1196/annals.1386.039
url = ]

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.cite journal
author = Hilakivi-Clarke L, Cho E, Onojafe I, Raygada M, Clarke R
title = Maternal exposure to genistein during pregnancy increases carcinogen-induced mammary tumorigenesis in female rat offspring
quote = 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.
journal = Oncol. Rep.
volume = 6
issue = 5
pages = 1089–95
year = 1999
pmid = 10425307
doi =
url =
issn = ]

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. [see discussion page] cite journal
author = Ju YH, Allred KF, Allred CD, Helferich WG
title = Genistein stimulates growth of human breast cancer cells in a novel, postmenopausal animal model, with low plasma estradiol concentrations
quote = Results from this study suggest that consumption of products containing GEN may not be safe for postmenopausal women with estrogen-dependent breast cancer.
journal = Carcinogenesis
volume = 27
issue = 6
pages = 1292–9
year = 2006
month = June
pmid = 16537557
doi = 10.1093/carcin/bgi370
url = ]

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. [ [http://www.westonaprice.org/mythstruths/mtvegetarianism.html#10 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. ]

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

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. [cite journal |author=Kumi-Diaka J, Rodriguez R, Goudaze G |title=Influence of genistein (4',5,7-trihydroxyisoflavone) on the growth and proliferation of testicular cell lines |journal=Biol. Cell |volume=90 |issue=4 |pages=349–54 |year=1998 |pmid=9800352
quote=Genistein-induced apoptosis identifies genistein as a potential diagnostic and therapeutic tool in testicular pathophysiological research. |doi=10.1016/S0248-4900(98)80015-4]

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 the CFTR channel, potentiating its opening at low concentration and inhibiting it a higher doses.

ources

Concentrations of genistein in "Pueraria mirifica" (White Kawo Krua) are so close to zero that experimental estimates of error equalled concentration measured. cite journal
author = Cherdshewasart W, Sriwatcharakul S
title = Major isoflavonoid contents of the 1-year-cultivated phytoestrogen-rich herb, Pueraria mirifica
journal = Biosci. Biotechnol. Biochem.
volume = 71
issue = 10
pages = 2527–33
year = 2007
month = October
pmid = 17928711
doi = 10.1271/bbb.70316
url = http://www.jstage.jst.go.jp/article/bbb/71/10/2527/_pdf ]

References