Genistein

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==Description==
==Description==
An isoflavonoid derived from soy products. It inhibits  PROTEIN-TYROSINE KINASE and topoisomerase-II (DNA TOPOISOMERASES, TYPE  II); activity and is used as an antineoplastic and antitumor agent.  Experimentally, it has been shown to induce G2 PHASE arrest in human  and murine cell lines and inhibits PROTEIN-TYROSINE KINASE.
An isoflavonoid derived from soy products. It inhibits  PROTEIN-TYROSINE KINASE and topoisomerase-II (DNA TOPOISOMERASES, TYPE  II); activity and is used as an antineoplastic and antitumor agent.  Experimentally, it has been shown to induce G2 PHASE arrest in human  and murine cell lines and inhibits PROTEIN-TYROSINE KINASE.
 +
 +
'''Genistein''' is one of several known [[isoflavone]]s. Isoflavones, such as genistein and [[daidzein]], are found in a number of [[plant]]s, with [[soybean]]s 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 [[antioxidant]]s, many isoflavones have been shown to interact with [[animal]] and [[human]] [[estrogen receptor]]s, 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]].<ref name="pmid15319357">{{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 = 
 +
}}</ref>
 +
 +
===Atherosclerosis===
 +
 +
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.<ref>http://www.bentham-direct.org/pages/content.php?CMC/2007/00000014/00000024/0007C.SGM</ref>
 +
 +
===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). However, Genistein has the effect of ''promoting'' breast cancer in one study.<ref name="pmid15126563">{{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 =
 +
}}</ref>
 +
 +
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.<ref name="pmid12667416">{{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 =
 +
}}</ref>
 +
 +
Timing of phytoestrogen use is important.<ref name="pmid17261753">{{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 = 
 +
}}</ref>
 +
 +
<!--Laboratory studies using animal models have shown that both soy and isoflavones can be protective against cancer when given during early life but can stimulate response to cancer-causing chemicals when given during fetal development or when circulating levels of estrogen are low ([[menopause]]).{{Fact|date=March 2008}} If you can't find it, and you know what you're doing, then snip this. The part about menopausal treatment is said elsewhere.-->Genistein makes some cells more sensitive to radio-therapy.<ref name="pmid17261753">{{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 = 
 +
}}</ref>
 +
 +
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.<ref name="pmid10425307">{{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 =
 +
}}</ref>
 +
 +
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. An animal study suggested that GEN may not be safe for postmenopausal women with estrogen-dependent breast cancer.<ref name="pmid16537557">{{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 = 
 +
}}</ref>
 +
 +
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.<ref>[http://www.westonaprice.org/mythstruths/mtvegetarianism.html#10 The Myths of Vegetarianism], Westin A. Price Foundation</ref>
 +
<ref>(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.
 +
</ref>
 +
 +
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.<ref>{{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
 +
}}</ref>
 +
 +
==Molecular function==
 +
Genistein influences several targets in living cells. One important function is the inhibition of several [[tyrosine kinase]]s. Genistein also inhibits the mammalian [[hexose]] transporter [[GLUT1]] and contraction of several types of [[smooth muscle]]s. Genistein can bind to the CFTR channel, potentiating its opening at low concentration and inhibiting it a higher doses.
 +
 +
==Sources==
 +
Concentrations of genistein in ''[[Pueraria mirifica]]'' (White Kawo Krua) are so close to zero that experimental estimates of error equalled concentration measured. <ref name="pmid17928711">{{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
 +
}}</ref>
==General Properties==
==General Properties==
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*[http://www.drugbank.ca/drugs/DB01645]Drugbank
*[http://www.drugbank.ca/drugs/DB01645]Drugbank
-
[[Categories:Hormones]]
+
[[Category:Phytochemicals]]
 +
[[Category:Dietary supplements]]
 +
[[Category:Nutrients]]
 +
[[Category:Flavonoids]]
 +
[[Category:Antioxidants]]
 +
[[Category:Hormones]]

Revision as of 11:52, 16 February 2009

Contents

Description

An isoflavonoid derived from soy products. It inhibits PROTEIN-TYROSINE KINASE and topoisomerase-II (DNA TOPOISOMERASES, TYPE II); activity and is used as an antineoplastic and antitumor agent. Experimentally, it has been shown to induce G2 PHASE arrest in human and murine cell lines and inhibits PROTEIN-TYROSINE KINASE.

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.<ref name="pmid15319357">Liu D, Homan LL, Dillon JS (December 2004). "Genistein acutely stimulates nitric oxide synthesis in vascular endothelial cells by a cyclic adenosine 5'-monophosphate-dependent mechanism". Endocrinology 145 (12): 5532–9. doi:10.1210/en.2004-0102. 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.” </ref>

Atherosclerosis

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.<ref>http://www.bentham-direct.org/pages/content.php?CMC/2007/00000014/00000024/0007C.SGM</ref>

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). However, Genistein has the effect of promoting breast cancer in one study.<ref name="pmid15126563">Chen WF, Wong MS (May 2004). "Genistein enhances insulin-like growth factor signaling pathway in human breast cancer (MCF-7) cells". J. Clin. Endocrinol. Metab. 89 (5): 2351–9. 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).” </ref>

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.<ref name="pmid12667416">Thomson CA, LeWinn K, Newton TR, Alberts DS, Martinez ME (May 2003). "Nutrition and diet in the development of gastrointestinal cancer". Curr Oncol Rep 5 (3): 192–202. PMID 12667416. “...the capacity for diet to alter Helicobacter pylori infection should be explored.” </ref>

Timing of phytoestrogen use is important.<ref name="pmid17261753">De Assis S, Hilakivi-Clarke L (November 2006). "Timing of dietary estrogenic exposures and breast cancer risk". Ann. N. Y. Acad. Sci. 1089: 14–35. doi:10.1196/annals.1386.039. 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.” </ref>

Genistein makes some cells more sensitive to radio-therapy.<ref name="pmid17261753">De Assis S, Hilakivi-Clarke L (November 2006). "Timing of dietary estrogenic exposures and breast cancer risk". Ann. N. Y. Acad. Sci. 1089: 14–35. doi:10.1196/annals.1386.039. PMID 17261753. “The viability was decreased by co-treatment with genistein and irradiation compared with irradiation treatment alone.” </ref>

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.<ref name="pmid10425307">Hilakivi-Clarke L, Cho E, Onojafe I, Raygada M, Clarke R (1999). "Maternal exposure to genistein during pregnancy increases carcinogen-induced mammary tumorigenesis in female rat offspring". Oncol. Rep. 6 (5): 1089–95. 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.” </ref>

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. An animal study suggested that GEN may not be safe for postmenopausal women with estrogen-dependent breast cancer.<ref name="pmid16537557">Ju YH, Allred KF, Allred CD, Helferich WG (June 2006). "Genistein stimulates growth of human breast cancer cells in a novel, postmenopausal animal model, with low plasma estradiol concentrations". Carcinogenesis 27 (6): 1292–9. doi:10.1093/carcin/bgi370. 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.” </ref>

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.<ref>The Myths of Vegetarianism, Westin A. Price Foundation</ref> <ref>(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. </ref>

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.<ref>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. doi:10.1016/S0248-4900(98)80015-4. PMID 9800352. “Genistein-induced apoptosis identifies genistein as a potential diagnostic and therapeutic tool in testicular pathophysiological research.” </ref>

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.

Sources

Concentrations of genistein in Pueraria mirifica (White Kawo Krua) are so close to zero that experimental estimates of error equalled concentration measured. <ref name="pmid17928711">Cherdshewasart W, Sriwatcharakul S (October 2007). "Major isoflavonoid contents of the 1-year-cultivated phytoestrogen-rich herb, Pueraria mirifica". Biosci. Biotechnol. Biochem. 71 (10): 2527–33. doi:10.1271/bbb.70316. PMID 17928711. </ref>

General Properties

*Molecular Weight

270.24

*Molecular Formula

C15H10O5

*IUPAC NAME

5,7-dihydroxy-3-(4-hydroxyphenyl)chromen-4-one

*Canonical Smiles

C1=CC(=CC=C1C2=COC3=CC(=CC(=C3C2=O)O)O)O

*Isomeric Smiles



PhysioChemical Properties

*Melting Point

301.5(EXP)

*LogP

2.84(EST)

*Water Solubility


External Links

  • [1]Pubchem
  • [2]KEGG Compound
  • [3]Human Metabolome DataBase
  • [4]Drugbank
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