Genistein: A multipurpose isoflavone

Ajay Gaur, Arvind Lal Bhatia

Abstract


Genistein is a soya isoflavone, mainly found in legumes, such as soybeans. Isoflavones may prove multipurpose biochemicals that have several functions such contribute colour to plant, protect the plant against bacterial and fungal infections, and serve a hormone-like role (as a phytooestrogen) in plant cell regulation. Scientists are discovering that when people eat soy products, such as tofu and soymilk, isoflavones and their derivatives produce health benefits in addition to nutritional values. Among various soya isoflavones, genistein has been shown to have a wide range of activities in animal models and experimental studies. On account of its tyrosine kinase inhibiting, antioxidant and oestrogenic or antioestrogenic activities as well as its p53 regulatory properties, researchers have been making endeavours in studying its effects against oxidative stress and related disorders. Convincing studies on its anticancer, lipid lowering, anti-diabetic, antiradiation, against eye diseases, against photodamage, against obesity and as well as immune system enhancers or stimulants have been heeded upon in the scientific world. This review reports some of the activities of genistein.
Key words: Genistein, soya isoflavone, soyabeans, antioxidants

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References


Fukutake M, Takahashi M, Ishida K, Kawamura H, Sugimura T,

Wakabayashi K. Quantification of Genistein in soyabeans and

soyabeans products. Food Chem Toxicol 1996;34:457-61.

Peterson TG, Ji GP, Kirk M, Coward L, Falany CN, Barnes S.

Metabolism of the isoflavones Genistein and biochanin A in human

breast cancer cell lines. Am J Clin Nutr 1998;68:1505-11.

Lamartiniere CA. Protection against breast cancer with Genistein:

a component of soy. Am J Clin Nutr 2000;71:1705-7.

Yellayi S, Naaz A, Szewczykowski MA, Sato T, Woods JA, Chang

J, et al. The phytoestrogen genistein induces thymic and immune

changes: A human health concern? Proc Nat Acad Sci USA

;99:7616-21.

Anupongsanugool E, Teekachunhatean S, Rojanasthien N,

Pongsatha S, Sangdee C. Pharmacokinetics of isoflavones, daidzein

and Genistein, after ingestion of soy beverage compared with

soy extract capsules in postmenopausal Thai women. BMC Clin

Pharmacol 2005;5:2.

Simon MA. Receptor tyrosine kinases: Specific outcomes from

general signals. Cell 2000;103:13-5.

Ravindranath MH, Muthugounder S, Presser N, Viswanathan, S.

Anticancer therapeutic potential of soy isoflavone, Genistein. Adv

Exp Med Biol 2004;546:121-65.

Belenky M, Prasain J, Kim H, Barnes S. DING, a genistein

target in human breast cancer: A protein without a gene. J Nutr

;133:2497-501.

Huang RQ, Dillon GH. Direct inhibition of glycine receptors

by Genistein, a tyrosine kinase inhibitor. Neuropharmacology

;39:2195-204.

Gould EM, Rembold CM, Murphy RA. Genistein, a tyrosine kinase

inhibitor, reduces Ca2+ mobilization in swine carotid media. Am

J Physiol 1995;268:1425-9.

Liao CH, Pan SL, Guh JH, Teng CM. Genistein inversely affects

tubulin-binding agent-induced apoptosis in human breast cancer

cells. Biochem Pharmacol 2004;67:2031-8.

Marverti G, Andrews PA. Stimulation of cisdiamminedichloroplatinum(

II) accumulation by modulation of passive permeability

with Genistein: An altered response in accumulation-defective

resistant cells. Clin Cancer Res 1996;2:991-9.

Wei H, Bowen R, Cai Q, Barnes S, Wang Y. Antioxidant and

antipromotional effects of the soybean isoflavone Genistein. Proc

Soc Exp Biol Med 1995;208:124-30.

Setchell KD. Phytoestrogen: The biochemistry, physiology, and

implications for human health of soya isoflavones. Am J Clin Nutr

;68:1333-46.

Zhang YC, Albrecht D, Bomer JS, Steven J, Vodovotz Y. Isoflavone

profile and biological activity of soya bread. J Agr Food Chem

;51:7611-6.

Arora A, Valcic S, Cornejo S, Nair MG, Timmermann BN, Liebler

DC. Reactions of genistein with alkylperoxyl radicals. Chem Res

Toxicol 2000;13:638-45.

Borrás C, Gambini J, Cabrera MC, Sastre J, Pallardó FV, Mann

GE, et al. Genistein, a soy isoflavone, up-regulates expression of

antioxidant genes: Involvement of estrogen receptors, ERK1/2,

and NF B. FASEB 2006;20:2136-8.

Santell RC, Chang YC, Nair MG, Helferich WG. Dietary Genistein

exerts estrogenic effects upon the uterus, mammary gland and the hypothalamic/pituitary axis in rats. J Nutr 1997;127:263-9.

Allerd CD, Allred KF, Ju YH, Clausen LM, Doerge DR, Schantz SL

et al. Dietary genistein results in larger MNU-induced, estrogendependent

mammary tumors following ovariectomy of Sprague–

Dawley rats. Carcinogenesis 2004;25:211-8.

Murray D. Aminothiols. In: Bump EA, Malaker K, editors.

Radioprotectors: Chemical, biological and clinical perspective.

Boca Raton, FL: CRC Press; 1998. p. 53-109.

Bouker KB, Clarke LH. Genistein: Does it prevent or promote breast

cancer? Environ Health Perspect 2000;108:701-8.

Makela S, Poutanen M, Kostian ML, Lehtimaki N, Strauss L, Santti

R, et al. Inhibition of 17-beta-hydroxysteroid oxidoreductase by

flavonoids in breast and prostate cancer cells. Proc Soc Exp Biol

Med 1998;217:310-6.

Miettinen M, Mustonen M, Poutanen M, Isomaa V, Vihko R. Human

-beta-hydroxysteroid dehydrogenase type 1 and 2 isoenzyme

have opposite activities in cultured cells and characteristic cell- and

tissue-specific expression. Biochem J 1996;314:839-45.

Poutanen M, Isomaa V, Peltoketo H, Vihko R. Role of 17-betahydroxysteroid

dehydrogenase type 1 in endocrine and intracrine

estradiol synthesis. J Steroid Biochem Mol Biol 1995;55:525-32.

Wang C, Makela T, Hase T, Adlercreutz H, Kurzer MS. Lignans and

isoflavonoids inhibit aromatase enzyme in human preadipocytes.

J Steroid Biochem Mol Biol 1994;50:205-12.

Schwartz JA, Liu G, Brooks SC. Genistein-mediated attenuation of

tamoxifen-induced antagonism from estrogen receptor-regulated

genes. Biochem Biophys Res Commun 1998;253:38-43.

Saki T, Kogiso M, Mitsuya K, Komatsu T, Yamamoto S. Genistein

enhances antigen-specific cytokine production in female DO11.10

transgenic mice. J Nutr Sci Vitaminol 2006;52:327-32.

Bhatia AL. Effects of radiation and genes mediated radiation

protection with special reference to melatonin. Presidential address

section: Anim Vet and Fish Sciences, 95th Indian Science Congress,

Vishakhapatnam 2008.

MacCallum DE, Happ TR, Midgley CA, Stuart D, Campbell SJ,

Harper A, et al. The p53 response to ionizing radiation in adult

and developing murine tissue. Oncogene 1996;13:2575-87.

Komarova EA, Chernov MV, Franks R, Wang K, Armin G, Zelnick

CR, et al. Transgenic mice with p53-responsive lacZ: p53 activity

varies dramatically during normal development and determines

radiation and drug sensitivity in vivo. EMBO J 1997;16:1391-400.

Gottlieb E, Haffner R, King A, Asher G, Gruss P, Lonai P,

et al. Transgenic mouse model for studying the transcriptional

activity of the p53 protein: Age and tissue dependent changes

in radiation-induced activation during embryogenesis. EMBO J

;16:1381-90.

Matsuoka S, Huang M, Elledge SJ. Linkage of ATM to cell cycle

regulation by the Chk2 protein kinase. Science 1998;282:1893-7.

Ruiqiong Y, Bodero A, Zhou BB, Khanna KK, Lavin MF, Miller

SPL. The plant isoflavenoid Genistein activates p53 and Chk2 in

an ATM-dependent Manner. J Biol Chem 2001;276:4828-33.

Murray D, McBride WH. Radioprotective agents. In: Kirk-Othmer,

editor. Encyclopedia of chemical technology. vol.20, 4th ed. New

York: Wiley; 1996. p. 963-1006.

Zava DT, Duwe G. Estrogenic and antiproliferative properties of

Genistein and other flavonoid in human breast cancer cells in vitro.

Nutr Cancer 1997;27:31-40.

Nakagawa H, Yamamoto D, Kiyozuka Y, Tsuta K, Uemura Y, Hioki

K, et al. Effects of Genistein and synergistic action in combination

with eicosapentaenoic acid on the growth of breast cancer celllines.

J Cancer Res Clin Oncol 2000;126:448-54.

Mizunuma H, Kanazawa K, Ogura S, Otsuka S, Nagai H.

Anticarcinogenic effects of isoflavones may be mediated by

genistein in mouse mammary tumor virus-induced breast cancer.

Oncology 2002;62:78-84.

Li Y, Sarkar FH. Down-regulation of invasion and angiogenesisrelated

genes identified by cDNA microarray analysis of

PC3 prostate cancer cells treated with Genistein. Cancer Lett

;186:157-64.

Suzuki K, Koike H, Matsui H. Genistein, a soy isoflavone, induces

glutathione peroxidase in the human prostate cancer cell lines

LNCaP and PC-3. Int J Cancer 2002;99:846-52.

Lian F, Bhuiyan M, Li YW, Wall N, Kraut M, Sarkar FH. Genisteininduced

G2-M arrest, p21WAF1 upregulation, and apoptosis in a

non-small-cell lung cancer cell line. Nutr Cancer 1998;31:184-191.

Jeong MH, Jin YH, Kang EY, Jo WS, Park HT, Lee JD, et al. The

modulation of radiation-induced cell death by Genistein in K562

cells: Activation of thymidine kinase 1. Cell Res 2004;14:295-302.

Shao ZM, Alpaugh ML, Fontana JA, Barsky SH. Genistein

inhibit proliferation in estrogen receptor-positive and negative

human breast carcinoma cell lines and apoptosis. J Cell Biochem

;69:44-54.

Yan SX, Ejima Y, Sasaki R, Zheng SS, Demizu Y, Soejima T, et al.

Combination of Genistein with ionizing radiation on androgenindependent

prostate cancer cells. Asian J Androl 2004;6:285-90.

Lamartiniere CA, Cotroneo MS, Fritz WA, Wang J, Mentor MR,

Elgavish A. Genistein chemoprevention timing and mechanism of

actions in murine mammary and prostate. J Nutr 2002;132:552-8.

Rao A, Woodruff RD, Wade WN, Kute TE, Cramer SD. Genistein

and vitamin D synergistically inhibit human prostatic epithelial

cell growth. J Nutr 2002;132:3191-4.

Clarke LH, Onojafe I, Raygada M, Cho E, Skaar T, Russo I, et

al. Prepubertal exposure to zearalenone or Genistein reduces

mammary tumorigenesis. Br J Cancer 1999;80;1682-8.

Rowell C, Carpenter DM, Lamartiniere CA. Chemoprevention of

breast cancer, proteomic discovery of genistein action in the rat

mammary gland. J Nutr 2005;135:2953-9.

Kim H, Xu J, Su Y. Actions of the soy phytoestrogen Genistein

in models of human chronic disease: Potential involvement

of transforming growth factor beta. Biochem Soc Trans

;29:216-22.

Yu Z, Li W, Liu F. Inhibition of proliferation and induction of

apoptosis by Genistein in colon cancer HT-29 cells. Cancer Lett

;215:159-66.

Gercel TC, Feitelson AK, Taylor DD. Inhibitory effect of Genistein

and daidzein on ovarian cancer cell growth. Anticancer Res

;24:795-800.

Yashar CM, Spanos WJ, Taylor DD, Taylor CG. Potentiation of the

radiation effect with Genistein in cervical cancer cells. Gynecol

Oncol 2005;99:199-205.

Yang Y, Zhou ZT, Ge JP. Effect of Genistein on DMBA-induced

oral carcinogenesis in hamster. Carcinogenesis 2006;27:578-83.

Anderson JJ, Ambrose WW, Garner SC. Orally dosed Genistein

from soy and prevention of cancellous bone loss in two

ovariectomized rat models. J Nutr 1995;125:799-807.

Anthony MS, Clarkson TB, Williams JK. Effects of soya isoflavones

on atherosclerosis: Potential mechanism. Am J Clin Nutr

;68:1390-4.

Potter SM, Baum JA, Teng H, Stillman RJ, Shang NF, Erdman

JW. Soya Proteins and Isoflavones: Their effects on blood lipids

and bone density in postmenopausal women. Am J Clin Nutr

;68:1375-9.

Naaz A, Yellayi S, Zakroczymski MA, Bunick D, Doerge DR,

Lubahn DB, et al. The soy isoflavone genistein decreases adipose

deposition in mice. Endocrinology 2003;144:3315-20.

Atteritano M, Marini H, Minutoli L, Polito F, Bitto A, Altavilla D,

et al. Effects of the phytoestrogen genistein on some predictors

of cardiovascular risk in osteopenic, postmenopausal women: A

two-year randomized, double-blind, placebo-controlled study. J

Clin Endocr Metab 2007;92:3068-75.

Chu L, Zhang JX, Norota I, Endoh M. Differential action of a protein

tyrosine kinase inhibitor, Genistein, on the positive inotropic

effect of endothelin-1 and norepinephrine in canine ventricular

myocardium. Br J Pharmacol 2005;144:430-42.

Pan W, Ikeda K, Takebe M, Yamori Y. Genistein, daidzein and

glycitein inhibit growth and DNA synthesis of aortic smooth

muscle cells from stroke-prone spontaneously hypertensive rats.

J Nutr 2001;131:1154-8.

Altavilla D, Crisafulli A, Marini H, Esposito M, Anna R, Corrado

F, et al. Cardiovascular effects of the phytoestrogen Genistein. Curr

Med Chem Cardiovasc Hematol Agents 2004;2:179-86.

Park SA, Sook CM, Yeul CS, Sook SJ, Jung UJ, Joo KM, et al.

Genistein and daidzein modulate hepatic glucose and lipid

regulating enzyme activities in C57BL/KsJ-db/db mice. Life Sci

;79:1207-13.

Hintz KK, Ren J. Phytoestrogenic isoflavones daidzein and

Genistein reduce glucose-toxicity-induced cardiac contractile

dysfunction in ventricular myocytes. Endocr Res 2004;30:215-23.

Hayashi A, Weinberger AW, Kim HC, Juan ED. Genistein, a protein

tyrosine kinase inhibitor, ameliorates retinal degeneration after

ischemia-reperfusion injury in rat. Investig Ophthalmol Visual

Sci 1997;38:1193-202.

Duan W, Kuo IC, Selvarajan S, Chua KY, Bay BH, Wong WS.

Antiinflammatory effects of genistein, a tyrosine kinase inhibitor,

on a guinea pig model of asthma. Am J Respir Crit Care Med

;167:185-92.

Wei H, Saladi R, Lu Y, Wang Y, Palep SR, Moore J, et al.

Isoflavone genistein: Photoprotection and clinical implications in

dermatology. J Nutr 2003;133:3811-9.

Wei H, Zhang X, Wang Y, Lebwohl M. Inhibition of ultraviolet

light-induced oxidative events in the skin and internal organs of

hairless mice by isoflavone Genistein. Cancer Lett 2002;185:21-9.

Kishida T, Nashiki K, Izumi T, Ebihara K. Soy isoflavonoid

aglycons genistein and daidzein do not increase the cytochrome

P-450 content of the liver microsomes of mice. Agric Food Chem

;48:3872-5.

Breinholt VM, Rasmussen SE, Brøsen K, Friedberg TH. In vitro

metabolism of genistein and tangeretin by human and murine

cytochrome P450s. Pharmacol Toxicol 2003;93:14-22.

Salas AL, Montezuma TD, Fariña GG, Esparza JR, Fragoso LR.

Genistein modifies liver fibrosis and improves liver function by

inducing uPA expression and proteolytic activity in CCl4-treated

rats. Pharmacology 2008;81:41-9.

Liu XJ, Yang L, Mao YQ, Wang Q, Huang MH, Wang YP, et al.

Effects of the tyrosine protein kinase inhibitor Genistein on the

proliferation, activation of cultured rat hepatic stellate cells. World

J Gastroenterol 2002;8:739-45.

Dolinoy DC, Weidman JR, Waterland RA, Jirtle RL. Maternal

genistein alters coat color and protects avy mouse offspring from

obesity by modifying the fetal epigenome. Environ Health Perspect

;114:567–72.

Greiner LL, Stahly TS, Stabel TJ. The effect of dietary soy Genistein

on pig growth and viral replication during a viral challenge. J Anim

Sci 2001;79:1272-9.

Banks EP, Jefferson WN, Newbold RR. Neonatal exposure to

the phytoestrogen genistein alters mammary gland growth

and developmental programming of hormone receptor levels.

Endocrinology 2006;20:1685.

Davis TA, Clarke TK, Mog SR, Landauer MR. Subcutaneous

administration of Genistein prior to lethal irradiation supports

multilineage, hematopoietic progenitor cell recovery and survival.

Int J Radiat Biol 2007;83:141–51.

Zhou Y, Man-Tian MI. Genistein stimulate as hematopoisis and

increases survivals in irradiated mice. J Radiat Res 2005;46:425-33.

Booth C, Hargreaves DF, Oshea JA, Potten CS. In vivo administration

of Genistein has no effect on small intestinal epithelial proliferation

and apoptosis, but a modest effect on clonogen survival. Cancer

Lett 1999;144:169-75.

Landauer MR, Srinivasan V, Shapiro A, Takimoto C, Seed TM.

Protection against lethal irradiation by Genistein. Int J Toxicol

;19:37.

Landauer MR, Srinivasan V, Grace MB, Chang CM, Parekh V,

Clarke TK, et al. Prevention of gamma radiation induced mortality

in mice by the isoflavone genistein. Paper presented at the NATO

human factors and medicine panel research task group “Radiation

bioeffects and counter measures†meeting, held in Bethesda, Md.,

USA, 2005.

Bhatia AL, Gaur A, Sharma A. Radiation protection by an

isoflavone Genistein: A study on the survivability of mice. Nucl

Tech Radiat Protect 2007;22:34-9.

Gaur A, Sharma A, Bhatia AL. Genistein against radiation damage:

A study on Swiss albino mice. Asian J Exp Sci 2006;20:269-73.




DOI: https://doi.org/10.22377/ijgp.v3i3.79

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