Home • Search • Translate
From Wikipedia, the free encyclopedia
Not to be confused with Genistin.
Genistein
Genistein molecule
Names
IUPAC name
4′,5,7-Trihydroxyisoflavone
Systematic IUPAC name
5,7-Dihydroxy-3-(4-hydroxyphenyl)-4H-1-benzopyran-4-one
Identifiers
3D model ( JSmol)
263823
ChEBI
ChEMBL
ChemSpider
DrugBank
ECHA InfoCard 100.006.524 Edit this at Wikidata
EC Number
  • 207-174-9
KEGG
PubChem CID
UNII
  • InChI=1S/C15H10O5/c16-9-3-1-8(2-4-9)11-7-20-13-6-10(17)5-12(18)14(13)15(11)19/h1-7,16-18H checkY
    Key: TZBJGXHYKVUXJN-UHFFFAOYSA-N checkY
  • InChI=1/C15H10O5/c16-9-3-1-8(2-4-9)11-7-20-13-6-10(17)5-12(18)14(13)15(11)19/h1-7,16-18H
    Key: TZBJGXHYKVUXJN-UHFFFAOYAH
  • Oc1ccc(cc1)C\3=C\Oc2cc(O)cc(O)c2C/3=O
Properties
C15H10O5
Molar mass 270.240 g·mol−1
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
checkY  verify ( what is checkY☒N ?)

Genistein (C15H10O5) is a naturally occurring compound that structurally belongs to a class of compounds known as isoflavones. It is described as an angiogenesis inhibitor and a phytoestrogen. [1]

It was first isolated in 1899 from the dyer's broom, Genista tinctoria; hence, the chemical name. The compound structure was established in 1926, when it was found to be identical with that of prunetol. It was chemically synthesized in 1928. [2] It has been shown to be the primary secondary metabolite of the Trifolium species and Glycine max. [3]

Natural occurrences

Isoflavones such as genistein and daidzein are found in a number of plants including lupin, fava beans, soybeans, kudzu, and psoralea being the primary food source, [4] [5] also in the medicinal plants, Flemingia vestita [6] and F. macrophylla, [7] [8] and coffee. [9] It can also be found in Maackia amurensis cell cultures. [10]

Biological effects

Besides functioning as an antioxidant and anthelmintic, 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. Isoflavones also produce non-hormonal effects.[ citation needed]

Molecular function

Genistein influences multiple biochemical functions in living cells:

Activation of PPARs

Isoflavones genistein and daidzein bind to and transactivate all three PPAR isoforms, α, δ, and γ. [20] 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. [21] 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. [20] [22] [23]

Tyrosine kinase inhibitor

The main known activity of genistein is tyrosine kinase inhibitor, mostly of epidermal growth factor receptor (EGFR). Tyrosine kinases are less widespread than their ser/thr counterparts but implicated in almost all cell growth and proliferation signal cascades.[ citation needed]

Redox-active—not only antioxidant

Genistein may act as direct antioxidant, similar to many other isoflavones, and thus may alleviate damaging effects of free radicals in tissues. [24] [25]

The same molecule of genistein, similar to many other isoflavones, by generation of free radicals poison topoisomerase II, an enzyme important for maintaining DNA stability. [26] [27] [28]

Human cells turn on beneficial, detoxifying Nrf2 factor in response to genistein insult. This pathway may be responsible for observed health maintaining properties of small doses of genistein. [29]

Anthelmintic

The root-tuber peel extract of the leguminous plant Flemingia vestita is the traditional anthelmintic of the Khasi tribes of India. While investigating its anthelmintic activity, genistein was found to be the major isoflavone responsible for the deworming property. [6] [30] Genistein was subsequently demonstrated to be highly effective against intestinal parasites such as the poultry cestode Raillietina echinobothrida, [30] the pork trematode Fasciolopsis buski, [31] and the sheep liver fluke Fasciola hepatica. [32] It exerts its anthelmintic activity by inhibiting the enzymes of glycolysis and glycogenolysis, [33] [34] and disturbing the Ca2+ homeostasis and NO activity in the parasites. [35] [36] It has also been investigated in human tapeworms such as Echinococcus multilocularis and E. granulosus metacestodes that genistein and its derivatives, Rm6423 and Rm6426, are potent cestocides. [37]

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. [38]

Cancer links

Genistein and other isoflavones have been identified as angiogenesis inhibitors, and found to inhibit the uncontrolled cell growth of cancer, most likely by inhibiting the activity of substances in the body that regulate cell division and cell survival ( growth factors). Various studies have found that moderate doses of genistein have inhibitory effects on cancers of the prostate, [39] [40] cervix, [41] brain, [42] breast [39] [43] [44] and colon. [17] It has also been shown that genistein makes some cells more sensitive to radio-therapy.; [45] although, timing of phytoestrogen use is also important. [45]

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. Inhibition of DNA topoisomerase II also plays an important role in the cytotoxic activity of genistein. [27] [46] The observation that transition of normal lymphocytes from quiescence (G0) to the G1 phase of the cell cycle is particularly sensitive to genistein prompted the authors to suggest that this isoflavone may be potential immunosuppressant. [47] Genistein has been used to selectively target pre B-cells via conjugation with an anti-CD19 antibody. [48]

Studies on rodents have found genistein to be useful in the treatment of leukemia, and that it can be used in combination with certain other antileukemic drugs to improve their efficacy. [49]

Estrogen receptor — more cancer links

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. [50]

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. [51] [52] [53] It was also found to decrease efficiency of tamoxifen and letrozole - drugs commonly used in breast cancer therapy. [54] [55] Genistein was found to inhibit immune response towards cancer cells allowing their survival. [56]

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 shown genistein to induce apoptosis of testicular cells at certain levels, thus raising concerns about effects it could have on male fertility; [57] however, one 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. [58]

Carcinogenic and toxic potential

Genistein was, among other flavonoids, found to be a strong topoisomerase inhibitor, similarly to some chemotherapeutic anticancer drugs ex. etoposide and doxorubicin. [26] [59] In high doses it was found to be strongly toxic to normal cells. [60] This effect may be responsible for both anticarcinogenic and carcinogenic potential of the substance. [28] [61] It was found to deteriorate DNA of cultured blood stem cells, which may lead to leukemia. [62] Genistein among other flavonoids is suspected to increase risk of infant leukemia when consumed during pregnancy. [63] [64]

Sanfilippo syndrome treatment

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. [65] Genistein was found to also possess toxic properties toward brain cells. [60] Among many pathways stimulated by genistein, autophagy may explain the observed efficiency of the substance as autophagy is significantly impaired in the disease. [66] [67]

Cognition

A study looking at Italians older than 50 found that those with the highest genistein intake had the lowest odds of cognitive impairment. [68]

Related compounds

See also

References

  1. ^ Sail, Vibhavari; Hadden, M. Kyle (2012-01-01), Desai, Manoj C. (ed.), Chapter Eighteen - Notch Pathway Modulators as Anticancer Chemotherapeutics, Annual Reports in Medicinal Chemistry, vol. 47, Academic Press, pp. 267–280, doi: 10.1016/B978-0-12-396492-2.00018-7, retrieved 2020-09-14
  2. ^ Walter, E. D. (1941). "Genistin (an Isoflavone Glucoside) and its Aglucone, Genistein, from Soybeans". Journal of the American Chemical Society. 63 (12): 3273–76. doi: 10.1021/ja01857a013.
  3. ^ Popiołkiewicz, Joanna; Polkowski, Krzysztof; Skierski, Janusz S.; Mazurek, Aleksander P. (November 2005). "In vitro toxicity evaluation in the development of new anticancer drugs—genistein glycosides". Cancer Letters. 229 (1): 67–75. doi: 10.1016/j.canlet.2005.01.014. ISSN  0304-3835. PMID  16157220.
  4. ^ Coward, Lori; Barnes, Neil C.; Setchell, Kenneth D. R.; Barnes, Stephen (1993). "Genistein, daidzein, and their β-glycoside conjugates: Antitumor isoflavones in soybean foods from American and Asian diets". Journal of Agricultural and Food Chemistry. 41 (11): 1961–7. doi: 10.1021/jf00035a027.
  5. ^ Kaufman, Peter B.; Duke, James A.; Brielmann, Harry; Boik, John; Hoyt, James E. (1997). "A Comparative Survey of Leguminous Plants as Sources of the Isoflavones, Genistein and Daidzein: Implications for Human Nutrition and Health". The Journal of Alternative and Complementary Medicine. 3 (1): 7–12. CiteSeerX  10.1.1.320.9747. doi: 10.1089/acm.1997.3.7. PMID  9395689.
  6. ^ a b Rao, H. S. P.; Reddy, K. S. (1991). "Isoflavones from Flemingia vestita". Fitoterapia. 62 (5): 458.
  7. ^ Rao, K.Nageswara; Srimannarayana, G. (1983). "Fleminone, a flavanone from the stems of Flemingia macrophylla". Phytochemistry. 22 (10): 2287–90. Bibcode: 1983PChem..22.2287R. doi: 10.1016/S0031-9422(00)80163-6.
  8. ^ Wang, Bor-Sen; Juang, Lih-Jeng; Yang, Jeng-Jer; Chen, Li-Ying; Tai, Huo-Mu; Huang, Ming-Hsing (2012). "Antioxidant and Antityrosinase Activity of Flemingia macrophylla and Glycine tomentella Roots". Evidence-Based Complementary and Alternative Medicine. 2012: 1–7. doi: 10.1155/2012/431081. PMC  3444970. PMID  22997529.
  9. ^ Alves, Rita C.; Almeida, Ivone M. C.; Casal, Susana; Oliveira, M. Beatriz P. P. (2010). "Isoflavones in Coffee: Influence of Species, Roast Degree, and Brewing Method". Journal of Agricultural and Food Chemistry. 58 (5): 3002–7. doi: 10.1021/jf9039205. PMID  20131840.
  10. ^ Fedoreyev, S.A; Pokushalova, T.V; Veselova, M.V; Glebko, L.I; Kulesh, N.I; Muzarok, T.I; Seletskaya, L.D; Bulgakov, V.P; Zhuravlev, Yu.N (2000). "Isoflavonoid production by callus cultures of Maackia amurensis". Fitoterapia. 71 (4): 365–72. doi: 10.1016/S0367-326X(00)00129-5. PMID  10925005.
  11. ^ Patisaul, Heather B.; Melby, Melissa; Whitten, Patricia L.; Young, Larry J. (2002). "Genistein Affects ERβ- But Not ERα-Dependent Gene Expression in the Hypothalamus". Endocrinology. 143 (6): 2189–2197. doi: 10.1210/endo.143.6.8843. ISSN  0013-7227. PMID  12021182.
  12. ^ Green, Sarah E (2015), In Vitro Comparison of Estrogenic Activities of Popular Women's Health Botanicals, archived from the original on 2016-02-22, retrieved 2016-01-01
  13. ^ Prossnitz ER, Arterburn JB (July 2015). "International Union of Basic and Clinical Pharmacology. XCVII. G Protein-Coupled Estrogen Receptor and Its Pharmacologic Modulators". Pharmacol. Rev. 67 (3): 505–40. doi: 10.1124/pr.114.009712. PMC  4485017. PMID  26023144.
  14. ^ Prossnitz, Eric R.; Barton, Matthias (2014). "Estrogen biology: New insights into GPER function and clinical opportunities". Molecular and Cellular Endocrinology. 389 (1–2): 71–83. doi: 10.1016/j.mce.2014.02.002. ISSN  0303-7207. PMC  4040308. PMID  24530924.
  15. ^ Gossner, G; Choi, M; Tan, L; Fogoros, S; Griffith, K; Kuenker, M; Liu, J (2007). "Genistein-induced apoptosis and autophagocytosis in ovarian cancer cells". Gynecologic Oncology. 105 (1): 23–30. doi: 10.1016/j.ygyno.2006.11.009. PMID  17234261.
  16. ^ Singletary, K.; Milner, J. (2008). "Diet, Autophagy, and Cancer: A Review". Cancer Epidemiology, Biomarkers & Prevention. 17 (7): 1596–610. doi: 10.1158/1055-9965.EPI-07-2917. PMID  18628411.
  17. ^ a b Nakamura, Yoshitaka; Yogosawa, Shingo; Izutani, Yasuyuki; Watanabe, Hirotsuna; Otsuji, Eigo; Sakai, Tosiyuki (2009). "A combination of indol-3-carbinol and genistein synergistically induces apoptosis in human colon cancer HT-29 cells by inhibiting Akt phosphorylation and progression of autophagy". Molecular Cancer. 8: 100. doi: 10.1186/1476-4598-8-100. PMC  2784428. PMID  19909554.
  18. ^ Fang, Mingzhu; Chen, Dapeng; Yang, Chung S. (January 2007). "Dietary polyphenols may affect DNA methylation". The Journal of Nutrition. 137 (1 Suppl): 223S–228S. doi: 10.1093/jn/137.1.223S. PMID  17182830.
  19. ^ Glushakov, A. V.; Glushakova, H. Y.; Skok, V. I. (1999-01-15). "Modulation of nicotinic acetylcholine receptor activity in submucous neurons by intracellular messengers". Journal of the Autonomic Nervous System. 75 (1): 16–22. doi: 10.1016/S0165-1838(98)00165-9. ISSN  0165-1838. PMID  9935265.
  20. ^ a b Wang, Limei; Waltenberger, Birgit; Pferschy-Wenzig, Eva-Maria; Blunder, Martina; Liu, Xin; Malainer, Clemens; Blazevic, Tina; Schwaiger, Stefan; Rollinger, Judith M.; Heiss, Elke H.; Schuster, Daniela; Kopp, Brigitte; Bauer, Rudolf; Stuppner, Hermann; Dirsch, Verena M.; Atanasov, Atanas G. (2014). "Natural product agonists of peroxisome proliferator-activated receptor gamma (PPARγ): A review". Biochemical Pharmacology. 92 (1): 73–89. doi: 10.1016/j.bcp.2014.07.018. PMC  4212005. PMID  25083916.
  21. ^ Dang, Zhi-Chao; Audinot, Valérie; Papapoulos, Socrates E.; Boutin, Jean A.; Löwik, Clemens W. G. M. (2002). "Peroxisome Proliferator-activated Receptor γ (PPARγ) as a Molecular Target for the Soy Phytoestrogen Genistein". Journal of Biological Chemistry. 278 (2): 962–7. doi: 10.1074/jbc.M209483200. PMID  12421816.
  22. ^ Dang, Zhi Chao; Lowik, Clemens (2005). "Dose-dependent effects of phytoestrogens on bone". Trends in Endocrinology and Metabolism. 16 (5): 207–13. doi: 10.1016/j.tem.2005.05.001. PMID  15922618. S2CID  35366615.
  23. ^ Dang, Z. C. (2009). "Dose-dependent effects of soy phyto-oestrogen genistein on adipocytes: Mechanisms of action". Obesity Reviews. 10 (3): 342–9. doi: 10.1111/j.1467-789X.2008.00554.x. PMID  19207876. S2CID  13804244.
  24. ^ Han, Rui-Min; Tian, Yu-Xi; Liu, Yin; Chen, Chang-Hui; Ai, Xi-Cheng; Zhang, Jian-Ping; Skibsted, Leif H. (2009). "Comparison of Flavonoids and Isoflavonoids as Antioxidants". Journal of Agricultural and Food Chemistry. 57 (9): 3780–5. doi: 10.1021/jf803850p. PMID  19296660.
  25. ^ Borrás, Consuelo; Gambini, Juan; López-Grueso, Raúl; Pallardó, Federico V.; Viña, Jose (2010). "Direct antioxidant and protective effect of estradiol on isolated mitochondria" (PDF). Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease. 1802 (1): 205–11. doi: 10.1016/j.bbadis.2009.09.007. PMID  19751829.
  26. ^ a b Bandele, Omari J.; Osheroff, Neil (2007). "Bioflavonoids as Poisons of Human Topoisomerase IIα and IIβ". Biochemistry. 46 (20): 6097–108. doi: 10.1021/bi7000664. PMC  2893030. PMID  17458941.
  27. ^ a b Markovits, Judith; Linassier, Claude; Fossé, Philippe; Couprie, Jeanine; Pierre, Josiane; Jacquemin-Sablon, Alain; Saucier, Jean-Marie; Le Pecq, Jean-Bernard; Larsen, Annette K. (September 1989). "Inhibitory effects of the tyrosine kinase inhibitor genistein on mammalian DNA topoisomerase II". Cancer Research. 49 (18): 5111–7. PMID  2548712.
  28. ^ a b López-Lázaro, Miguel; Willmore, Elaine; Austin, Caroline A. (2007). "Cells Lacking DNA Topoisomerase IIβ are Resistant to Genistein". Journal of Natural Products. 70 (5): 763–7. doi: 10.1021/np060609z. PMID  17411092.
  29. ^ Mann, Giovanni E; Bonacasa, Barbara; Ishii, Tetsuro; Siow, Richard CM (2009). "Targeting the redox sensitive Nrf2–Keap1 defense pathway in cardiovascular disease: Protection afforded by dietary isoflavones". Current Opinion in Pharmacology. 9 (2): 139–45. doi: 10.1016/j.coph.2008.12.012. PMID  19157984.
  30. ^ a b Tandon, V.; Pal, P.; Roy, B.; Rao, H. S. P.; Reddy, K. S. (1997). "In vitro anthelmintic activity of root-tuber extract of Flemingia vestita, an indigenous plant in Shillong, India". Parasitology Research. 83 (5): 492–8. doi: 10.1007/s004360050286. PMID  9197399. S2CID  25086153.
  31. ^ Kar, Pradip K; Tandon, Veena; Saha, Nirmalendu (2002). "Anthelmintic efficacy of Flemingia vestita: Genistein-induced effect on the activity of nitric oxide synthase and nitric oxide in the trematode parasite, Fasciolopsis buski". Parasitology International. 51 (3): 249–57. doi: 10.1016/S1383-5769(02)00032-6. PMID  12243779.
  32. ^ Toner, E.; Brennan, G. P.; Wells, K.; McGeown, J. G.; Fairweather, I. (2008). "Physiological and morphological effects of genistein against the liver fluke, Fasciola hepatica". Parasitology. 135 (10): 1189–203. doi: 10.1017/S0031182008004630. PMID  18771609. S2CID  6525410.
  33. ^ Tandon, Veena; Das, Bidyadhar; Saha, Nirmalendu (2003). "Anthelmintic efficacy of Flemingia vestita (Fabaceae): Effect of genistein on glycogen metabolism in the cestode, Raillietina echinobothrida". Parasitology International. 52 (2): 179–86. doi: 10.1016/S1383-5769(03)00006-0. PMID  12798931.
  34. ^ Das, B.; Tandon, V.; Saha, N. (2004). "Anthelmintic efficacy of Flemingia vestita (Fabaceae): Alteration in the activities of some glycolytic enzymes in the cestode, Raillietina echinobothrida". Parasitology Research. 93 (4): 253–61. doi: 10.1007/s00436-004-1122-8. PMID  15138892. S2CID  9491127.
  35. ^ Das, Bidyadhar; Tandon, Veena; Saha, Nirmalendu (2006). "Effect of isoflavone from Flemingia vestita (Fabaceae) on the Ca2+ homeostasis in Raillietina echinobothrida, the cestode of domestic fowl". Parasitology International. 55 (1): 17–21. doi: 10.1016/j.parint.2005.08.002. PMID  16198617.
  36. ^ Das, Bidyadhar; Tandon, Veena; Lyndem, Larisha M.; Gray, Alexander I.; Ferro, Valerie A. (2009). "Phytochemicals from Flemingia vestita (Fabaceae) and Stephania glabra (Menispermeaceae) alter cGMP concentration in the cestode Raillietina echinobothrida". Comparative Biochemistry and Physiology C. 149 (3): 397–403. doi: 10.1016/j.cbpc.2008.09.012. PMID  18854226.
  37. ^ Naguleswaran, Arunasalam; Spicher, Martin; Vonlaufen, Nathalie; Ortega-Mora, Luis M.; Torgerson, Paul; Gottstein, Bruno; Hemphill, Andrew (2006). "In Vitro Metacestodicidal Activities of Genistein and Other Isoflavones against Echinococcus multilocularis and Echinococcus granulosus". Antimicrobial Agents and Chemotherapy. 50 (11): 3770–8. doi: 10.1128/AAC.00578-06. PMC  1635224. PMID  16954323.
  38. ^ Si, Hongwei; Liu, Dongmin; Si, Hongwei; Liu, Dongmin (2007). "Phytochemical Genistein in the Regulation of Vascular Function: New Insights". Current Medicinal Chemistry. 14 (24): 2581–9. doi: 10.2174/092986707782023325. PMID  17979711.
  39. ^ a b Morito, Keiko; Hirose, Toshiharu; Kinjo, Junei; Hirakawa, Tomoki; Okawa, Masafumi; Nohara, Toshihiro; Ogawa, Sumito; Inoue, Satoshi; Muramatsu, Masami; Masamune, Yukito (2001). "Interaction of Phytoestrogens with Estrogen Receptors α and β". Biological & Pharmaceutical Bulletin. 24 (4): 351–6. doi: 10.1248/bpb.24.351. PMID  11305594.
  40. ^ Hwang, Ye Won; Kim, Soo Young; Jee, Sun Ha; Kim, Youn Nam; Nam, Chung Mo (2009). "Soy Food Consumption and Risk of Prostate Cancer: A Meta-Analysis of Observational Studies". Nutrition and Cancer. 61 (5): 598–606. doi: 10.1080/01635580902825639. PMID  19838933. S2CID  19719873.
  41. ^ Kim, Su-Hyeon; Kim, Su-Hyeong; Kim, Yong-Beom; Jeon, Yong-Tark; Lee, Sang-Chul; Song, Yong-Sang (2009). "Genistein Inhibits Cell Growth by Modulating Various Mitogen-Activated Protein Kinases and AKT in Cervical Cancer Cells". Annals of the New York Academy of Sciences. 1171 (1): 495–500. Bibcode: 2009NYASA1171..495K. doi: 10.1111/j.1749-6632.2009.04899.x. PMID  19723095. S2CID  26111697.
  42. ^ Das, Arabinda; Banik, Naren L.; Ray, Swapan K. (2009). "Flavonoids activated caspases for apoptosis in human glioblastoma T98G and U87MG cells but not in human normal astrocytes". Cancer. 116 (1): 164–76. doi: 10.1002/cncr.24699. PMC  3159962. PMID  19894226.
  43. ^ Sakamoto, Takako; Horiguchi, Hyogo; Oguma, Etsuko; Kayama, Fujio (2010). "Effects of diverse dietary phytoestrogens on cell growth, cell cycle and apoptosis in estrogen-receptor-positive breast cancer cells". The Journal of Nutritional Biochemistry. 21 (9): 856–64. doi: 10.1016/j.jnutbio.2009.06.010. PMID  19800779.
  44. ^ de Lemos, Mário L (2001). "Effects of Soy Phytoestrogens Genistein and Daidzein on Breast Cancer Growth". The Annals of Pharmacotherapy. 35 (9): 1118–21. doi: 10.1345/aph.10257. PMID  11573864. S2CID  208876381.
  45. ^ a b de Assis, Sonia; Hilakivi-Clarke, Leena (2006). "Timing of Dietary Estrogenic Exposures and Breast Cancer Risk". Annals of the New York Academy of Sciences. 1089 (1): 14–35. Bibcode: 2006NYASA1089...14D. doi: 10.1196/annals.1386.039. PMID  17261753. S2CID  22170442.
  46. ^ López-Lázaro, Miguel; Willmore, Elaine; Austin, Caroline A. (2007). "Cells Lacking DNA Topoisomerase IIβ are Resistant to Genistein". Journal of Natural Products. 70 (5): 763–7. doi: 10.1021/np060609z. PMID  17411092.
  47. ^ Traganos, F; Ardelt, B; Halko, N; Bruno, S; Darzynkiewicz, Z (1992). "Effects of genistein on the growth and cell cycle progression of normal human lymphocytes and human leukemic MOLT-4 and HL-60 cells". Cancer Res. 52 (22): 6200–8. PMID  1330289.
  48. ^ Safa, Malek; Foon, Kenneth A.; Oldham, Robert K. (2009). "Drug Immunoconjugates". In Oldham, Robert K.; Dillman, Robert O. (eds.). Principles of Cancer Biotherapy (5th ed.). pp. 451–62. doi: 10.1007/978-90-481-2289-9_12. ISBN  978-90-481-2277-6.
  49. ^ Raynal, Noël J. M.; Charbonneau, Michel; Momparler, Louise F.; Momparler, Richard L. (2008). "Synergistic Effect of 5-Aza-2′-Deoxycytidine and Genistein in Combination Against Leukemia". Oncology Research Featuring Preclinical and Clinical Cancer Therapeutics. 17 (5): 223–30. doi: 10.3727/096504008786111356. PMID  18980019.
  50. ^ Kuiper, George G. J. M.; Lemmen, Josephine G.; Carlsson, Bo; Corton, J. Christopher; Safe, Stephen H.; van der Saag, Paul T.; van der Burg, Bart; Gustafsson, Jan-Åke (1998). "Interaction of Estrogenic Chemicals and Phytoestrogens with Estrogen Receptor β". Endocrinology. 139 (10): 4252–63. doi: 10.1210/endo.139.10.6216. PMID  9751507.
  51. ^ Ju, Young H.; Allred, Kimberly F.; Allred, Clinton D.; Helferich, William G. (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.
  52. ^ Chen, Wen-Fang; Wong, Man-Sau (2004). "Genistein Enhances Insulin-Like Growth Factor Signaling Pathway in Human Breast Cancer (MCF-7) Cells". The Journal of Clinical Endocrinology & Metabolism. 89 (5): 2351–9. doi: 10.1210/jc.2003-032065. PMID  15126563.
  53. ^ Yang, Xiaohe; Yang, Shihe; McKimmey, Christine; Liu, Bolin; Edgerton, Susan M.; Bales, Wesley; Archer, Linda T.; Thor, Ann D. (2010). "Genistein induces enhanced growth promotion in ER-positive/erbB-2-overexpressing breast cancers by ER-erbB-2 cross talk and p27/kip1 downregulation". Carcinogenesis. 31 (4): 695–702. doi: 10.1093/carcin/bgq007. PMID  20067990.
  54. ^ Helferich, W. G.; Andrade, J. E.; Hoagland, M. S. (2008). "Phytoestrogens and breast cancer: A complex story". Inflammopharmacology. 16 (5): 219–26. doi: 10.1007/s10787-008-8020-0. PMID  18815740. S2CID  11659490.
  55. ^ Tonetti, Debra A.; Zhang, Yiyun; Zhao, Huiping; Lim, Sok-Bee; Constantinou, Andreas I. (2007). "The Effect of the Phytoestrogens Genistein, Daidzein, and Equol on the Growth of Tamoxifen-Resistant T47D/PKCα". Nutrition and Cancer. 58 (2): 222–9. doi: 10.1080/01635580701328545. PMID  17640169. S2CID  10831895.
  56. ^ Jiang, Xinguo; Patterson, Nicole M.; Ling, Yan; Xie, Jianwei; Helferich, William G.; Shapiro, David J. (2008). "Low Concentrations of the Soy Phytoestrogen Genistein Induce Proteinase Inhibitor 9 and Block Killing of Breast Cancer Cells by Immune Cells". Endocrinology. 149 (11): 5366–73. doi: 10.1210/en.2008-0857. PMC  2584580. PMID  18669594.
  57. ^ Kumi-Diaka, James; Rodriguez, Rosanna; Goudaze, Gould (1998). "Influence of genistein (4′,5,7-trihydroxyisoflavone) on the growth and proliferation of testicular cell lines". Biology of the Cell. 90 (4): 349–54. doi: 10.1016/S0248-4900(98)80015-4. PMID  9800352.
  58. ^ Mitchell, Julie H.; Cawood, Elizabeth; Kinniburgh, David; Provan, Anne; Collins, Andrew R.; Irvine, D. Stewart (2001). "Effect of a phytoestrogen food supplement on reproductive health in normal males". Clinical Science. 100 (6): 613–8. doi: 10.1042/CS20000212. PMID  11352776.
  59. ^ Lutz, Werner K.; Tiedge, Oliver; Lutz, Roman W.; Stopper, Helga (2005). "Different Types of Combination Effects for the Induction of Micronuclei in Mouse Lymphoma Cells by Binary Mixtures of the Genotoxic Agents MMS, MNU, and Genistein". Toxicological Sciences. 86 (2): 318–23. doi: 10.1093/toxsci/kfi200. hdl: 20.500.11850/32271. PMID  15901918.
  60. ^ a b Jin, Ying; Wu, Heng; Cohen, Eric M.; Wei, Jianning; Jin, Hong; Prentice, Howard; Wu, Jang-Yen (2007). "Genistein and daidzein induce neurotoxicity at high concentrations in primary rat neuronal cultures". Journal of Biomedical Science. 14 (2): 275–84. doi: 10.1007/s11373-006-9142-2. PMID  17245525.
  61. ^ Schmidt, Friederike; Knobbe, Christiane; Frank, Brigitte; Wolburg, Hartwig; Weller, Michael (2008). "The topoisomerase II inhibitor, genistein, induces G2/M arrest and apoptosis in human malignant glioma cell lines". Oncology Reports. 19 (4): 1061–6. doi: 10.3892/or.19.4.1061. PMID  18357397.
  62. ^ van Waalwijk van Doorn-Khosrovani, Sahar Barjesteh; Janssen, Jannie; Maas, Lou M.; Godschalk, Roger W. L.; Nijhuis, Jan G.; van Schooten, Frederik J. (2007). "Dietary flavonoids induce MLL translocations in primary human CD34+ cells". Carcinogenesis. 28 (8): 1703–9. doi: 10.1093/carcin/bgm102. PMID  17468513.
  63. ^ Spector, Logan G.; Xie, Yang; Robison, Leslie L.; Heerema, Nyla A.; Hilden, Joanne M.; Lange, Beverly; Felix, Carolyn A.; Davies, Stella M.; Slavin, Joanne; Potter, John D.; Blair, Cindy K.; Reaman, Gregory H.; Ross, Julie A. (2005). "Maternal Diet and Infant Leukemia: The DNA Topoisomerase II Inhibitor Hypothesis: A Report from the Children's Oncology Group". Cancer Epidemiology, Biomarkers & Prevention. 14 (3): 651–5. doi: 10.1158/1055-9965.EPI-04-0602. PMID  15767345.
  64. ^ Azarova, Anna M.; Lin, Ren-Kuo; Tsai, Yuan-Chin; Liu, Leroy F.; Lin, Chao-Po; Lyu, Yi Lisa (2010). "Genistein induces topoisomerase IIbeta- and proteasome-mediated DNA sequence rearrangements: Implications in infant leukemia". Biochemical and Biophysical Research Communications. 399 (1): 66–71. doi: 10.1016/j.bbrc.2010.07.043. PMC  3376163. PMID  20638367.
  65. ^ Piotrowska, Ewa; Jakóbkiewicz-Banecka, Joanna; Barańska, Sylwia; Tylki-Szymańska, Anna; Czartoryska, Barbara; Węgrzyn, Alicja; Węgrzyn, Grzegorz (2006). "Genistein-mediated inhibition of glycosaminoglycan synthesis as a basis for gene expression-targeted isoflavone therapy for mucopolysaccharidoses". European Journal of Human Genetics. 14 (7): 846–52. doi: 10.1038/sj.ejhg.5201623. PMID  16670689.
  66. ^ Ballabio, A. (2009). "Disease pathogenesis explained by basic science: Lysosomal storage diseases as autophagocytic disorders". International Journal of Clinical Pharmacology and Therapeutics. 47 (Suppl 1): S34–8. doi: 10.5414/cpp47034. PMID  20040309.
  67. ^ Settembre, Carmine; Fraldi, Alessandro; Jahreiss, Luca; Spampanato, Carmine; Venturi, Consuelo; Medina, Diego; de Pablo, Raquel; Tacchetti, Carlo; Rubinsztein, David C.; Ballabio, Andrea (2007). "A block of autophagy in lysosomal storage disorders". Human Molecular Genetics. 17 (1): 119–29. doi: 10.1093/hmg/ddm289. PMID  17913701.
  68. ^ Giampieri, Francesca; Godos, Justyna; Caruso, Giuseppe; Owczarek, Marcin; Jurek, Joanna; Castellano, Sabrina; Ferri, Raffaele; Caraci, Filippo; Grosso, Giuseppe (2022-05-30). "Dietary Phytoestrogen Intake and Cognitive Status in Southern Italian Older Adults". Biomolecules. 12 (6): 760. doi: 10.3390/biom12060760. ISSN  2218-273X. PMC  9221352. PMID  35740885.
  69. ^ Xu, Li; Farmer, Rebecca; Huang, Xiaoke; Pavese, Janet; Voll, Eric; Irene, Ogden; Biddle, Margaret; Nibbs, Antoinette; Valsecchi, Matias; Scheidt, Karl; Bergan, Raymond (2010). "Abstract B58: Discovery of a novel drug KBU2046 that inhibits conversion of human prostate cancer to a metastatic phenotype". Cancer Prevention Research. 3 (12 Supplement): B58. doi: 10.1158/1940-6207.PREV-10-B58.
  70. ^ "New Drug Stops Spread of Prostate Cancer" (Press release). Northwestern University. April 3, 2012. Retrieved September 27, 2014.
  71. ^ Chen, Chun-Lin; Levine, Alexandra; Rao, Asha; O'Neill, Karen; Messinger, Yoav; Myers, Dorothea E.; Goldman, Frederick; Hurvitz, Carole; Casper, James T.; Uckun, Fatih M. (1999). "Clinical Pharmacokinetics of the CD19 Receptor-Directed Tyrosine Kinase Inhibitor B43-Genistein in Patients with B-Lineage Lymphoid Malignancies". The Journal of Clinical Pharmacology. 39 (12): 1248–55. doi: 10.1177/00912709922012051. PMID  10586390. S2CID  24445516.

External links

Wikimedia Commons has media related to Genistein.
Retrieved from " https://en.wikipedia.org/?title=Genistein&oldid=1193517445"
From Wikipedia, the free encyclopedia
Not to be confused with Genistin.
Genistein
Genistein molecule
Names
IUPAC name
4′,5,7-Trihydroxyisoflavone
Systematic IUPAC name
5,7-Dihydroxy-3-(4-hydroxyphenyl)-4H-1-benzopyran-4-one
Identifiers
3D model ( JSmol)
263823
ChEBI
ChEMBL
ChemSpider
DrugBank
ECHA InfoCard 100.006.524 Edit this at Wikidata
EC Number
  • 207-174-9
KEGG
PubChem CID
UNII
  • InChI=1S/C15H10O5/c16-9-3-1-8(2-4-9)11-7-20-13-6-10(17)5-12(18)14(13)15(11)19/h1-7,16-18H checkY
    Key: TZBJGXHYKVUXJN-UHFFFAOYSA-N checkY
  • InChI=1/C15H10O5/c16-9-3-1-8(2-4-9)11-7-20-13-6-10(17)5-12(18)14(13)15(11)19/h1-7,16-18H
    Key: TZBJGXHYKVUXJN-UHFFFAOYAH
  • Oc1ccc(cc1)C\3=C\Oc2cc(O)cc(O)c2C/3=O
Properties
C15H10O5
Molar mass 270.240 g·mol−1
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
checkY  verify ( what is checkY☒N ?)

Genistein (C15H10O5) is a naturally occurring compound that structurally belongs to a class of compounds known as isoflavones. It is described as an angiogenesis inhibitor and a phytoestrogen. [1]

It was first isolated in 1899 from the dyer's broom, Genista tinctoria; hence, the chemical name. The compound structure was established in 1926, when it was found to be identical with that of prunetol. It was chemically synthesized in 1928. [2] It has been shown to be the primary secondary metabolite of the Trifolium species and Glycine max. [3]

Natural occurrences

Isoflavones such as genistein and daidzein are found in a number of plants including lupin, fava beans, soybeans, kudzu, and psoralea being the primary food source, [4] [5] also in the medicinal plants, Flemingia vestita [6] and F. macrophylla, [7] [8] and coffee. [9] It can also be found in Maackia amurensis cell cultures. [10]

Biological effects

Besides functioning as an antioxidant and anthelmintic, 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. Isoflavones also produce non-hormonal effects.[ citation needed]

Molecular function

Genistein influences multiple biochemical functions in living cells:

Activation of PPARs

Isoflavones genistein and daidzein bind to and transactivate all three PPAR isoforms, α, δ, and γ. [20] 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. [21] 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. [20] [22] [23]

Tyrosine kinase inhibitor

The main known activity of genistein is tyrosine kinase inhibitor, mostly of epidermal growth factor receptor (EGFR). Tyrosine kinases are less widespread than their ser/thr counterparts but implicated in almost all cell growth and proliferation signal cascades.[ citation needed]

Redox-active—not only antioxidant

Genistein may act as direct antioxidant, similar to many other isoflavones, and thus may alleviate damaging effects of free radicals in tissues. [24] [25]

The same molecule of genistein, similar to many other isoflavones, by generation of free radicals poison topoisomerase II, an enzyme important for maintaining DNA stability. [26] [27] [28]

Human cells turn on beneficial, detoxifying Nrf2 factor in response to genistein insult. This pathway may be responsible for observed health maintaining properties of small doses of genistein. [29]

Anthelmintic

The root-tuber peel extract of the leguminous plant Flemingia vestita is the traditional anthelmintic of the Khasi tribes of India. While investigating its anthelmintic activity, genistein was found to be the major isoflavone responsible for the deworming property. [6] [30] Genistein was subsequently demonstrated to be highly effective against intestinal parasites such as the poultry cestode Raillietina echinobothrida, [30] the pork trematode Fasciolopsis buski, [31] and the sheep liver fluke Fasciola hepatica. [32] It exerts its anthelmintic activity by inhibiting the enzymes of glycolysis and glycogenolysis, [33] [34] and disturbing the Ca2+ homeostasis and NO activity in the parasites. [35] [36] It has also been investigated in human tapeworms such as Echinococcus multilocularis and E. granulosus metacestodes that genistein and its derivatives, Rm6423 and Rm6426, are potent cestocides. [37]

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. [38]

Cancer links

Genistein and other isoflavones have been identified as angiogenesis inhibitors, and found to inhibit the uncontrolled cell growth of cancer, most likely by inhibiting the activity of substances in the body that regulate cell division and cell survival ( growth factors). Various studies have found that moderate doses of genistein have inhibitory effects on cancers of the prostate, [39] [40] cervix, [41] brain, [42] breast [39] [43] [44] and colon. [17] It has also been shown that genistein makes some cells more sensitive to radio-therapy.; [45] although, timing of phytoestrogen use is also important. [45]

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. Inhibition of DNA topoisomerase II also plays an important role in the cytotoxic activity of genistein. [27] [46] The observation that transition of normal lymphocytes from quiescence (G0) to the G1 phase of the cell cycle is particularly sensitive to genistein prompted the authors to suggest that this isoflavone may be potential immunosuppressant. [47] Genistein has been used to selectively target pre B-cells via conjugation with an anti-CD19 antibody. [48]

Studies on rodents have found genistein to be useful in the treatment of leukemia, and that it can be used in combination with certain other antileukemic drugs to improve their efficacy. [49]

Estrogen receptor — more cancer links

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. [50]

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. [51] [52] [53] It was also found to decrease efficiency of tamoxifen and letrozole - drugs commonly used in breast cancer therapy. [54] [55] Genistein was found to inhibit immune response towards cancer cells allowing their survival. [56]

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 shown genistein to induce apoptosis of testicular cells at certain levels, thus raising concerns about effects it could have on male fertility; [57] however, one 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. [58]

Carcinogenic and toxic potential

Genistein was, among other flavonoids, found to be a strong topoisomerase inhibitor, similarly to some chemotherapeutic anticancer drugs ex. etoposide and doxorubicin. [26] [59] In high doses it was found to be strongly toxic to normal cells. [60] This effect may be responsible for both anticarcinogenic and carcinogenic potential of the substance. [28] [61] It was found to deteriorate DNA of cultured blood stem cells, which may lead to leukemia. [62] Genistein among other flavonoids is suspected to increase risk of infant leukemia when consumed during pregnancy. [63] [64]

Sanfilippo syndrome treatment

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. [65] Genistein was found to also possess toxic properties toward brain cells. [60] Among many pathways stimulated by genistein, autophagy may explain the observed efficiency of the substance as autophagy is significantly impaired in the disease. [66] [67]

Cognition

A study looking at Italians older than 50 found that those with the highest genistein intake had the lowest odds of cognitive impairment. [68]

Related compounds

See also

References

  1. ^ Sail, Vibhavari; Hadden, M. Kyle (2012-01-01), Desai, Manoj C. (ed.), Chapter Eighteen - Notch Pathway Modulators as Anticancer Chemotherapeutics, Annual Reports in Medicinal Chemistry, vol. 47, Academic Press, pp. 267–280, doi: 10.1016/B978-0-12-396492-2.00018-7, retrieved 2020-09-14
  2. ^ Walter, E. D. (1941). "Genistin (an Isoflavone Glucoside) and its Aglucone, Genistein, from Soybeans". Journal of the American Chemical Society. 63 (12): 3273–76. doi: 10.1021/ja01857a013.
  3. ^ Popiołkiewicz, Joanna; Polkowski, Krzysztof; Skierski, Janusz S.; Mazurek, Aleksander P. (November 2005). "In vitro toxicity evaluation in the development of new anticancer drugs—genistein glycosides". Cancer Letters. 229 (1): 67–75. doi: 10.1016/j.canlet.2005.01.014. ISSN  0304-3835. PMID  16157220.
  4. ^ Coward, Lori; Barnes, Neil C.; Setchell, Kenneth D. R.; Barnes, Stephen (1993). "Genistein, daidzein, and their β-glycoside conjugates: Antitumor isoflavones in soybean foods from American and Asian diets". Journal of Agricultural and Food Chemistry. 41 (11): 1961–7. doi: 10.1021/jf00035a027.
  5. ^ Kaufman, Peter B.; Duke, James A.; Brielmann, Harry; Boik, John; Hoyt, James E. (1997). "A Comparative Survey of Leguminous Plants as Sources of the Isoflavones, Genistein and Daidzein: Implications for Human Nutrition and Health". The Journal of Alternative and Complementary Medicine. 3 (1): 7–12. CiteSeerX  10.1.1.320.9747. doi: 10.1089/acm.1997.3.7. PMID  9395689.
  6. ^ a b Rao, H. S. P.; Reddy, K. S. (1991). "Isoflavones from Flemingia vestita". Fitoterapia. 62 (5): 458.
  7. ^ Rao, K.Nageswara; Srimannarayana, G. (1983). "Fleminone, a flavanone from the stems of Flemingia macrophylla". Phytochemistry. 22 (10): 2287–90. Bibcode: 1983PChem..22.2287R. doi: 10.1016/S0031-9422(00)80163-6.
  8. ^ Wang, Bor-Sen; Juang, Lih-Jeng; Yang, Jeng-Jer; Chen, Li-Ying; Tai, Huo-Mu; Huang, Ming-Hsing (2012). "Antioxidant and Antityrosinase Activity of Flemingia macrophylla and Glycine tomentella Roots". Evidence-Based Complementary and Alternative Medicine. 2012: 1–7. doi: 10.1155/2012/431081. PMC  3444970. PMID  22997529.
  9. ^ Alves, Rita C.; Almeida, Ivone M. C.; Casal, Susana; Oliveira, M. Beatriz P. P. (2010). "Isoflavones in Coffee: Influence of Species, Roast Degree, and Brewing Method". Journal of Agricultural and Food Chemistry. 58 (5): 3002–7. doi: 10.1021/jf9039205. PMID  20131840.
  10. ^ Fedoreyev, S.A; Pokushalova, T.V; Veselova, M.V; Glebko, L.I; Kulesh, N.I; Muzarok, T.I; Seletskaya, L.D; Bulgakov, V.P; Zhuravlev, Yu.N (2000). "Isoflavonoid production by callus cultures of Maackia amurensis". Fitoterapia. 71 (4): 365–72. doi: 10.1016/S0367-326X(00)00129-5. PMID  10925005.
  11. ^ Patisaul, Heather B.; Melby, Melissa; Whitten, Patricia L.; Young, Larry J. (2002). "Genistein Affects ERβ- But Not ERα-Dependent Gene Expression in the Hypothalamus". Endocrinology. 143 (6): 2189–2197. doi: 10.1210/endo.143.6.8843. ISSN  0013-7227. PMID  12021182.
  12. ^ Green, Sarah E (2015), In Vitro Comparison of Estrogenic Activities of Popular Women's Health Botanicals, archived from the original on 2016-02-22, retrieved 2016-01-01
  13. ^ Prossnitz ER, Arterburn JB (July 2015). "International Union of Basic and Clinical Pharmacology. XCVII. G Protein-Coupled Estrogen Receptor and Its Pharmacologic Modulators". Pharmacol. Rev. 67 (3): 505–40. doi: 10.1124/pr.114.009712. PMC  4485017. PMID  26023144.
  14. ^ Prossnitz, Eric R.; Barton, Matthias (2014). "Estrogen biology: New insights into GPER function and clinical opportunities". Molecular and Cellular Endocrinology. 389 (1–2): 71–83. doi: 10.1016/j.mce.2014.02.002. ISSN  0303-7207. PMC  4040308. PMID  24530924.
  15. ^ Gossner, G; Choi, M; Tan, L; Fogoros, S; Griffith, K; Kuenker, M; Liu, J (2007). "Genistein-induced apoptosis and autophagocytosis in ovarian cancer cells". Gynecologic Oncology. 105 (1): 23–30. doi: 10.1016/j.ygyno.2006.11.009. PMID  17234261.
  16. ^ Singletary, K.; Milner, J. (2008). "Diet, Autophagy, and Cancer: A Review". Cancer Epidemiology, Biomarkers & Prevention. 17 (7): 1596–610. doi: 10.1158/1055-9965.EPI-07-2917. PMID  18628411.
  17. ^ a b Nakamura, Yoshitaka; Yogosawa, Shingo; Izutani, Yasuyuki; Watanabe, Hirotsuna; Otsuji, Eigo; Sakai, Tosiyuki (2009). "A combination of indol-3-carbinol and genistein synergistically induces apoptosis in human colon cancer HT-29 cells by inhibiting Akt phosphorylation and progression of autophagy". Molecular Cancer. 8: 100. doi: 10.1186/1476-4598-8-100. PMC  2784428. PMID  19909554.
  18. ^ Fang, Mingzhu; Chen, Dapeng; Yang, Chung S. (January 2007). "Dietary polyphenols may affect DNA methylation". The Journal of Nutrition. 137 (1 Suppl): 223S–228S. doi: 10.1093/jn/137.1.223S. PMID  17182830.
  19. ^ Glushakov, A. V.; Glushakova, H. Y.; Skok, V. I. (1999-01-15). "Modulation of nicotinic acetylcholine receptor activity in submucous neurons by intracellular messengers". Journal of the Autonomic Nervous System. 75 (1): 16–22. doi: 10.1016/S0165-1838(98)00165-9. ISSN  0165-1838. PMID  9935265.
  20. ^ a b Wang, Limei; Waltenberger, Birgit; Pferschy-Wenzig, Eva-Maria; Blunder, Martina; Liu, Xin; Malainer, Clemens; Blazevic, Tina; Schwaiger, Stefan; Rollinger, Judith M.; Heiss, Elke H.; Schuster, Daniela; Kopp, Brigitte; Bauer, Rudolf; Stuppner, Hermann; Dirsch, Verena M.; Atanasov, Atanas G. (2014). "Natural product agonists of peroxisome proliferator-activated receptor gamma (PPARγ): A review". Biochemical Pharmacology. 92 (1): 73–89. doi: 10.1016/j.bcp.2014.07.018. PMC  4212005. PMID  25083916.
  21. ^ Dang, Zhi-Chao; Audinot, Valérie; Papapoulos, Socrates E.; Boutin, Jean A.; Löwik, Clemens W. G. M. (2002). "Peroxisome Proliferator-activated Receptor γ (PPARγ) as a Molecular Target for the Soy Phytoestrogen Genistein". Journal of Biological Chemistry. 278 (2): 962–7. doi: 10.1074/jbc.M209483200. PMID  12421816.
  22. ^ Dang, Zhi Chao; Lowik, Clemens (2005). "Dose-dependent effects of phytoestrogens on bone". Trends in Endocrinology and Metabolism. 16 (5): 207–13. doi: 10.1016/j.tem.2005.05.001. PMID  15922618. S2CID  35366615.
  23. ^ Dang, Z. C. (2009). "Dose-dependent effects of soy phyto-oestrogen genistein on adipocytes: Mechanisms of action". Obesity Reviews. 10 (3): 342–9. doi: 10.1111/j.1467-789X.2008.00554.x. PMID  19207876. S2CID  13804244.
  24. ^ Han, Rui-Min; Tian, Yu-Xi; Liu, Yin; Chen, Chang-Hui; Ai, Xi-Cheng; Zhang, Jian-Ping; Skibsted, Leif H. (2009). "Comparison of Flavonoids and Isoflavonoids as Antioxidants". Journal of Agricultural and Food Chemistry. 57 (9): 3780–5. doi: 10.1021/jf803850p. PMID  19296660.
  25. ^ Borrás, Consuelo; Gambini, Juan; López-Grueso, Raúl; Pallardó, Federico V.; Viña, Jose (2010). "Direct antioxidant and protective effect of estradiol on isolated mitochondria" (PDF). Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease. 1802 (1): 205–11. doi: 10.1016/j.bbadis.2009.09.007. PMID  19751829.
  26. ^ a b Bandele, Omari J.; Osheroff, Neil (2007). "Bioflavonoids as Poisons of Human Topoisomerase IIα and IIβ". Biochemistry. 46 (20): 6097–108. doi: 10.1021/bi7000664. PMC  2893030. PMID  17458941.
  27. ^ a b Markovits, Judith; Linassier, Claude; Fossé, Philippe; Couprie, Jeanine; Pierre, Josiane; Jacquemin-Sablon, Alain; Saucier, Jean-Marie; Le Pecq, Jean-Bernard; Larsen, Annette K. (September 1989). "Inhibitory effects of the tyrosine kinase inhibitor genistein on mammalian DNA topoisomerase II". Cancer Research. 49 (18): 5111–7. PMID  2548712.
  28. ^ a b López-Lázaro, Miguel; Willmore, Elaine; Austin, Caroline A. (2007). "Cells Lacking DNA Topoisomerase IIβ are Resistant to Genistein". Journal of Natural Products. 70 (5): 763–7. doi: 10.1021/np060609z. PMID  17411092.
  29. ^ Mann, Giovanni E; Bonacasa, Barbara; Ishii, Tetsuro; Siow, Richard CM (2009). "Targeting the redox sensitive Nrf2–Keap1 defense pathway in cardiovascular disease: Protection afforded by dietary isoflavones". Current Opinion in Pharmacology. 9 (2): 139–45. doi: 10.1016/j.coph.2008.12.012. PMID  19157984.
  30. ^ a b Tandon, V.; Pal, P.; Roy, B.; Rao, H. S. P.; Reddy, K. S. (1997). "In vitro anthelmintic activity of root-tuber extract of Flemingia vestita, an indigenous plant in Shillong, India". Parasitology Research. 83 (5): 492–8. doi: 10.1007/s004360050286. PMID  9197399. S2CID  25086153.
  31. ^ Kar, Pradip K; Tandon, Veena; Saha, Nirmalendu (2002). "Anthelmintic efficacy of Flemingia vestita: Genistein-induced effect on the activity of nitric oxide synthase and nitric oxide in the trematode parasite, Fasciolopsis buski". Parasitology International. 51 (3): 249–57. doi: 10.1016/S1383-5769(02)00032-6. PMID  12243779.
  32. ^ Toner, E.; Brennan, G. P.; Wells, K.; McGeown, J. G.; Fairweather, I. (2008). "Physiological and morphological effects of genistein against the liver fluke, Fasciola hepatica". Parasitology. 135 (10): 1189–203. doi: 10.1017/S0031182008004630. PMID  18771609. S2CID  6525410.
  33. ^ Tandon, Veena; Das, Bidyadhar; Saha, Nirmalendu (2003). "Anthelmintic efficacy of Flemingia vestita (Fabaceae): Effect of genistein on glycogen metabolism in the cestode, Raillietina echinobothrida". Parasitology International. 52 (2): 179–86. doi: 10.1016/S1383-5769(03)00006-0. PMID  12798931.
  34. ^ Das, B.; Tandon, V.; Saha, N. (2004). "Anthelmintic efficacy of Flemingia vestita (Fabaceae): Alteration in the activities of some glycolytic enzymes in the cestode, Raillietina echinobothrida". Parasitology Research. 93 (4): 253–61. doi: 10.1007/s00436-004-1122-8. PMID  15138892. S2CID  9491127.
  35. ^ Das, Bidyadhar; Tandon, Veena; Saha, Nirmalendu (2006). "Effect of isoflavone from Flemingia vestita (Fabaceae) on the Ca2+ homeostasis in Raillietina echinobothrida, the cestode of domestic fowl". Parasitology International. 55 (1): 17–21. doi: 10.1016/j.parint.2005.08.002. PMID  16198617.
  36. ^ Das, Bidyadhar; Tandon, Veena; Lyndem, Larisha M.; Gray, Alexander I.; Ferro, Valerie A. (2009). "Phytochemicals from Flemingia vestita (Fabaceae) and Stephania glabra (Menispermeaceae) alter cGMP concentration in the cestode Raillietina echinobothrida". Comparative Biochemistry and Physiology C. 149 (3): 397–403. doi: 10.1016/j.cbpc.2008.09.012. PMID  18854226.
  37. ^ Naguleswaran, Arunasalam; Spicher, Martin; Vonlaufen, Nathalie; Ortega-Mora, Luis M.; Torgerson, Paul; Gottstein, Bruno; Hemphill, Andrew (2006). "In Vitro Metacestodicidal Activities of Genistein and Other Isoflavones against Echinococcus multilocularis and Echinococcus granulosus". Antimicrobial Agents and Chemotherapy. 50 (11): 3770–8. doi: 10.1128/AAC.00578-06. PMC  1635224. PMID  16954323.
  38. ^ Si, Hongwei; Liu, Dongmin; Si, Hongwei; Liu, Dongmin (2007). "Phytochemical Genistein in the Regulation of Vascular Function: New Insights". Current Medicinal Chemistry. 14 (24): 2581–9. doi: 10.2174/092986707782023325. PMID  17979711.
  39. ^ a b Morito, Keiko; Hirose, Toshiharu; Kinjo, Junei; Hirakawa, Tomoki; Okawa, Masafumi; Nohara, Toshihiro; Ogawa, Sumito; Inoue, Satoshi; Muramatsu, Masami; Masamune, Yukito (2001). "Interaction of Phytoestrogens with Estrogen Receptors α and β". Biological & Pharmaceutical Bulletin. 24 (4): 351–6. doi: 10.1248/bpb.24.351. PMID  11305594.
  40. ^ Hwang, Ye Won; Kim, Soo Young; Jee, Sun Ha; Kim, Youn Nam; Nam, Chung Mo (2009). "Soy Food Consumption and Risk of Prostate Cancer: A Meta-Analysis of Observational Studies". Nutrition and Cancer. 61 (5): 598–606. doi: 10.1080/01635580902825639. PMID  19838933. S2CID  19719873.
  41. ^ Kim, Su-Hyeon; Kim, Su-Hyeong; Kim, Yong-Beom; Jeon, Yong-Tark; Lee, Sang-Chul; Song, Yong-Sang (2009). "Genistein Inhibits Cell Growth by Modulating Various Mitogen-Activated Protein Kinases and AKT in Cervical Cancer Cells". Annals of the New York Academy of Sciences. 1171 (1): 495–500. Bibcode: 2009NYASA1171..495K. doi: 10.1111/j.1749-6632.2009.04899.x. PMID  19723095. S2CID  26111697.
  42. ^ Das, Arabinda; Banik, Naren L.; Ray, Swapan K. (2009). "Flavonoids activated caspases for apoptosis in human glioblastoma T98G and U87MG cells but not in human normal astrocytes". Cancer. 116 (1): 164–76. doi: 10.1002/cncr.24699. PMC  3159962. PMID  19894226.
  43. ^ Sakamoto, Takako; Horiguchi, Hyogo; Oguma, Etsuko; Kayama, Fujio (2010). "Effects of diverse dietary phytoestrogens on cell growth, cell cycle and apoptosis in estrogen-receptor-positive breast cancer cells". The Journal of Nutritional Biochemistry. 21 (9): 856–64. doi: 10.1016/j.jnutbio.2009.06.010. PMID  19800779.
  44. ^ de Lemos, Mário L (2001). "Effects of Soy Phytoestrogens Genistein and Daidzein on Breast Cancer Growth". The Annals of Pharmacotherapy. 35 (9): 1118–21. doi: 10.1345/aph.10257. PMID  11573864. S2CID  208876381.
  45. ^ a b de Assis, Sonia; Hilakivi-Clarke, Leena (2006). "Timing of Dietary Estrogenic Exposures and Breast Cancer Risk". Annals of the New York Academy of Sciences. 1089 (1): 14–35. Bibcode: 2006NYASA1089...14D. doi: 10.1196/annals.1386.039. PMID  17261753. S2CID  22170442.
  46. ^ López-Lázaro, Miguel; Willmore, Elaine; Austin, Caroline A. (2007). "Cells Lacking DNA Topoisomerase IIβ are Resistant to Genistein". Journal of Natural Products. 70 (5): 763–7. doi: 10.1021/np060609z. PMID  17411092.
  47. ^ Traganos, F; Ardelt, B; Halko, N; Bruno, S; Darzynkiewicz, Z (1992). "Effects of genistein on the growth and cell cycle progression of normal human lymphocytes and human leukemic MOLT-4 and HL-60 cells". Cancer Res. 52 (22): 6200–8. PMID  1330289.
  48. ^ Safa, Malek; Foon, Kenneth A.; Oldham, Robert K. (2009). "Drug Immunoconjugates". In Oldham, Robert K.; Dillman, Robert O. (eds.). Principles of Cancer Biotherapy (5th ed.). pp. 451–62. doi: 10.1007/978-90-481-2289-9_12. ISBN  978-90-481-2277-6.
  49. ^ Raynal, Noël J. M.; Charbonneau, Michel; Momparler, Louise F.; Momparler, Richard L. (2008). "Synergistic Effect of 5-Aza-2′-Deoxycytidine and Genistein in Combination Against Leukemia". Oncology Research Featuring Preclinical and Clinical Cancer Therapeutics. 17 (5): 223–30. doi: 10.3727/096504008786111356. PMID  18980019.
  50. ^ Kuiper, George G. J. M.; Lemmen, Josephine G.; Carlsson, Bo; Corton, J. Christopher; Safe, Stephen H.; van der Saag, Paul T.; van der Burg, Bart; Gustafsson, Jan-Åke (1998). "Interaction of Estrogenic Chemicals and Phytoestrogens with Estrogen Receptor β". Endocrinology. 139 (10): 4252–63. doi: 10.1210/endo.139.10.6216. PMID  9751507.
  51. ^ Ju, Young H.; Allred, Kimberly F.; Allred, Clinton D.; Helferich, William G. (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.
  52. ^ Chen, Wen-Fang; Wong, Man-Sau (2004). "Genistein Enhances Insulin-Like Growth Factor Signaling Pathway in Human Breast Cancer (MCF-7) Cells". The Journal of Clinical Endocrinology & Metabolism. 89 (5): 2351–9. doi: 10.1210/jc.2003-032065. PMID  15126563.
  53. ^ Yang, Xiaohe; Yang, Shihe; McKimmey, Christine; Liu, Bolin; Edgerton, Susan M.; Bales, Wesley; Archer, Linda T.; Thor, Ann D. (2010). "Genistein induces enhanced growth promotion in ER-positive/erbB-2-overexpressing breast cancers by ER-erbB-2 cross talk and p27/kip1 downregulation". Carcinogenesis. 31 (4): 695–702. doi: 10.1093/carcin/bgq007. PMID  20067990.
  54. ^ Helferich, W. G.; Andrade, J. E.; Hoagland, M. S. (2008). "Phytoestrogens and breast cancer: A complex story". Inflammopharmacology. 16 (5): 219–26. doi: 10.1007/s10787-008-8020-0. PMID  18815740. S2CID  11659490.
  55. ^ Tonetti, Debra A.; Zhang, Yiyun; Zhao, Huiping; Lim, Sok-Bee; Constantinou, Andreas I. (2007). "The Effect of the Phytoestrogens Genistein, Daidzein, and Equol on the Growth of Tamoxifen-Resistant T47D/PKCα". Nutrition and Cancer. 58 (2): 222–9. doi: 10.1080/01635580701328545. PMID  17640169. S2CID  10831895.
  56. ^ Jiang, Xinguo; Patterson, Nicole M.; Ling, Yan; Xie, Jianwei; Helferich, William G.; Shapiro, David J. (2008). "Low Concentrations of the Soy Phytoestrogen Genistein Induce Proteinase Inhibitor 9 and Block Killing of Breast Cancer Cells by Immune Cells". Endocrinology. 149 (11): 5366–73. doi: 10.1210/en.2008-0857. PMC  2584580. PMID  18669594.
  57. ^ Kumi-Diaka, James; Rodriguez, Rosanna; Goudaze, Gould (1998). "Influence of genistein (4′,5,7-trihydroxyisoflavone) on the growth and proliferation of testicular cell lines". Biology of the Cell. 90 (4): 349–54. doi: 10.1016/S0248-4900(98)80015-4. PMID  9800352.
  58. ^ Mitchell, Julie H.; Cawood, Elizabeth; Kinniburgh, David; Provan, Anne; Collins, Andrew R.; Irvine, D. Stewart (2001). "Effect of a phytoestrogen food supplement on reproductive health in normal males". Clinical Science. 100 (6): 613–8. doi: 10.1042/CS20000212. PMID  11352776.
  59. ^ Lutz, Werner K.; Tiedge, Oliver; Lutz, Roman W.; Stopper, Helga (2005). "Different Types of Combination Effects for the Induction of Micronuclei in Mouse Lymphoma Cells by Binary Mixtures of the Genotoxic Agents MMS, MNU, and Genistein". Toxicological Sciences. 86 (2): 318–23. doi: 10.1093/toxsci/kfi200. hdl: 20.500.11850/32271. PMID  15901918.
  60. ^ a b Jin, Ying; Wu, Heng; Cohen, Eric M.; Wei, Jianning; Jin, Hong; Prentice, Howard; Wu, Jang-Yen (2007). "Genistein and daidzein induce neurotoxicity at high concentrations in primary rat neuronal cultures". Journal of Biomedical Science. 14 (2): 275–84. doi: 10.1007/s11373-006-9142-2. PMID  17245525.
  61. ^ Schmidt, Friederike; Knobbe, Christiane; Frank, Brigitte; Wolburg, Hartwig; Weller, Michael (2008). "The topoisomerase II inhibitor, genistein, induces G2/M arrest and apoptosis in human malignant glioma cell lines". Oncology Reports. 19 (4): 1061–6. doi: 10.3892/or.19.4.1061. PMID  18357397.
  62. ^ van Waalwijk van Doorn-Khosrovani, Sahar Barjesteh; Janssen, Jannie; Maas, Lou M.; Godschalk, Roger W. L.; Nijhuis, Jan G.; van Schooten, Frederik J. (2007). "Dietary flavonoids induce MLL translocations in primary human CD34+ cells". Carcinogenesis. 28 (8): 1703–9. doi: 10.1093/carcin/bgm102. PMID  17468513.
  63. ^ Spector, Logan G.; Xie, Yang; Robison, Leslie L.; Heerema, Nyla A.; Hilden, Joanne M.; Lange, Beverly; Felix, Carolyn A.; Davies, Stella M.; Slavin, Joanne; Potter, John D.; Blair, Cindy K.; Reaman, Gregory H.; Ross, Julie A. (2005). "Maternal Diet and Infant Leukemia: The DNA Topoisomerase II Inhibitor Hypothesis: A Report from the Children's Oncology Group". Cancer Epidemiology, Biomarkers & Prevention. 14 (3): 651–5. doi: 10.1158/1055-9965.EPI-04-0602. PMID  15767345.
  64. ^ Azarova, Anna M.; Lin, Ren-Kuo; Tsai, Yuan-Chin; Liu, Leroy F.; Lin, Chao-Po; Lyu, Yi Lisa (2010). "Genistein induces topoisomerase IIbeta- and proteasome-mediated DNA sequence rearrangements: Implications in infant leukemia". Biochemical and Biophysical Research Communications. 399 (1): 66–71. doi: 10.1016/j.bbrc.2010.07.043. PMC  3376163. PMID  20638367.
  65. ^ Piotrowska, Ewa; Jakóbkiewicz-Banecka, Joanna; Barańska, Sylwia; Tylki-Szymańska, Anna; Czartoryska, Barbara; Węgrzyn, Alicja; Węgrzyn, Grzegorz (2006). "Genistein-mediated inhibition of glycosaminoglycan synthesis as a basis for gene expression-targeted isoflavone therapy for mucopolysaccharidoses". European Journal of Human Genetics. 14 (7): 846–52. doi: 10.1038/sj.ejhg.5201623. PMID  16670689.
  66. ^ Ballabio, A. (2009). "Disease pathogenesis explained by basic science: Lysosomal storage diseases as autophagocytic disorders". International Journal of Clinical Pharmacology and Therapeutics. 47 (Suppl 1): S34–8. doi: 10.5414/cpp47034. PMID  20040309.
  67. ^ Settembre, Carmine; Fraldi, Alessandro; Jahreiss, Luca; Spampanato, Carmine; Venturi, Consuelo; Medina, Diego; de Pablo, Raquel; Tacchetti, Carlo; Rubinsztein, David C.; Ballabio, Andrea (2007). "A block of autophagy in lysosomal storage disorders". Human Molecular Genetics. 17 (1): 119–29. doi: 10.1093/hmg/ddm289. PMID  17913701.
  68. ^ Giampieri, Francesca; Godos, Justyna; Caruso, Giuseppe; Owczarek, Marcin; Jurek, Joanna; Castellano, Sabrina; Ferri, Raffaele; Caraci, Filippo; Grosso, Giuseppe (2022-05-30). "Dietary Phytoestrogen Intake and Cognitive Status in Southern Italian Older Adults". Biomolecules. 12 (6): 760. doi: 10.3390/biom12060760. ISSN  2218-273X. PMC  9221352. PMID  35740885.
  69. ^ Xu, Li; Farmer, Rebecca; Huang, Xiaoke; Pavese, Janet; Voll, Eric; Irene, Ogden; Biddle, Margaret; Nibbs, Antoinette; Valsecchi, Matias; Scheidt, Karl; Bergan, Raymond (2010). "Abstract B58: Discovery of a novel drug KBU2046 that inhibits conversion of human prostate cancer to a metastatic phenotype". Cancer Prevention Research. 3 (12 Supplement): B58. doi: 10.1158/1940-6207.PREV-10-B58.
  70. ^ "New Drug Stops Spread of Prostate Cancer" (Press release). Northwestern University. April 3, 2012. Retrieved September 27, 2014.
  71. ^ Chen, Chun-Lin; Levine, Alexandra; Rao, Asha; O'Neill, Karen; Messinger, Yoav; Myers, Dorothea E.; Goldman, Frederick; Hurvitz, Carole; Casper, James T.; Uckun, Fatih M. (1999). "Clinical Pharmacokinetics of the CD19 Receptor-Directed Tyrosine Kinase Inhibitor B43-Genistein in Patients with B-Lineage Lymphoid Malignancies". The Journal of Clinical Pharmacology. 39 (12): 1248–55. doi: 10.1177/00912709922012051. PMID  10586390. S2CID  24445516.

External links

Wikimedia Commons has media related to Genistein.
Retrieved from " https://en.wikipedia.org/?title=Genistein&oldid=1193517445"

Videos

Youtube | Vimeo | Bing

Websites

Google | Yahoo | Bing

Encyclopedia

Google | Yahoo | Bing

Facebook




Top Of Page

Home • Search • Translate

© CSE