Genistein (C
15H
10O
5) is a naturally occurring compound that structurally belongs to a class of compounds known as
isoflavones. It is described as an
angiogenesis inhibitor An angiogenesis inhibitor is a substance that inhibits the growth of new blood vessels (angiogenesis). Some angiogenesis inhibitors are endogenous and a normal part of the body's control and others are obtained exogenously through drugs, pharmaceuti ...
and a
phytoestrogen
A phytoestrogen is a plant-derived xenoestrogen (see estrogen) not generated within the endocrine system, but consumed by eating plants or manufactured foods. Also called a "dietary estrogen", it is a diverse group of naturally occurring nonstero ...
.
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. It has been shown to be the primary secondary metabolite of the ''Trifolium'' species and ''Glycine max L''.
Natural occurrences
Isoflavones such as genistein and
daidzein
Daidzein (7-hydroxy-3-(4-hydroxyphenyl)-4H-chromen-4-one) is a naturally occurring compound found exclusively in soybeans and other legumes and structurally belongs to a class of compounds known as isoflavones. Daidzein and other isoflavones ar ...
are found in a number of plants including
lupin
''Lupinus'', commonly known as lupin, lupine, or regionally bluebonnet etc., is a genus of plants in the legume family Fabaceae. The genus includes over 199 species, with centers of diversity in North and South America. Smaller centers occur ...
,
fava bean
''Vicia faba'', commonly known as the broad bean, fava bean, or faba bean, is a species of vetch, a flowering plant in the pea and bean family Fabaceae. It is widely cultivated as a crop for human consumption, and also as a cover crop. Var ...
s,
soybean
The soybean, soy bean, or soya bean (''Glycine max'') is a species of legume native to East Asia, widely grown for its edible bean, which has numerous uses.
Traditional unfermented food uses of soybeans include soy milk, from which tofu an ...
s,
kudzu
Kudzu (; also called Japanese arrowroot or Chinese arrowroot) is a group of climbing, coiling, and trailing deciduous perennial vines native to much of East Asia, Southeast Asia, and some Pacific islands, but invasive species, invasive in many ...
, and
psoralea
''Psoralea'' is a genus in the legume family (Fabaceae) with over 60 closely related species native to southern Africa. In South Africa they are commonly referred to as fountainbush (English); fonteinbos, bloukeur, or penwortel (Afrikaans); and u ...
being the primary food source, also in the
medicinal plant
Medicinal plants, also called medicinal herbs, have been discovered and used in traditional medicine practices since prehistoric times. Plants synthesize hundreds of chemical compounds for various functions, including Plant defense against her ...
s, ''
Flemingia vestita''
and ''
F. macrophylla'', and
coffee
Coffee is a drink prepared from roasted coffee beans. Darkly colored, bitter, and slightly acidic, coffee has a stimulant, stimulating effect on humans, primarily due to its caffeine content. It is the most popular hot drink in the world.
S ...
. It can also be found in ''
Maackia amurensis
''Maackia amurensis'', commonly known as the Amur maackia, is a species of tree in the family Fabaceae that can grow 15 metres (49 ft) tall. The species epithet and common names are from the Amur River region, where the tree originated; it o ...
'' cell cultures.
Biological effects
Besides functioning as an
antioxidant
Antioxidants are compounds that inhibit oxidation, a chemical reaction that can produce free radicals. This can lead to polymerization and other chain reactions. They are frequently added to industrial products, such as fuels and lubricant ...
and
anthelmintic
Anthelmintics or antihelminthics are a group of antiparasitic drugs that expel parasitic worms (helminths) and other internal parasites from the body by either stunning or killing them and without causing significant damage to the host. They may a ...
, many
isoflavone Isoflavones are substituted derivatives of isoflavone, a type of naturally occurring isoflavonoids, many of which act as phytoestrogens in mammals. Isoflavones are produced almost exclusively by the members of the bean family, Fabaceae (Leguminosae ...
s have been shown to interact with
animal
Animals are multicellular, eukaryotic organisms in the Kingdom (biology), biological kingdom Animalia. With few exceptions, animals Heterotroph, consume organic material, Cellular respiration#Aerobic respiration, breathe oxygen, are Motilit ...
and
human
Humans (''Homo sapiens'') are the most abundant and widespread species of primate, characterized by bipedalism and exceptional cognitive skills due to a large and complex brain. This has enabled the development of advanced tools, culture, ...
estrogen receptor
Estrogen receptors (ERs) are a group of proteins found inside cells. They are receptors that are activated by the hormone estrogen ( 17β-estradiol). Two classes of ER exist: nuclear estrogen receptors (ERα and ERβ), which are members of the ...
s, causing effects in the body similar to those caused by the
hormone estrogen.
Isoflavone Isoflavones are substituted derivatives of isoflavone, a type of naturally occurring isoflavonoids, many of which act as phytoestrogens in mammals. Isoflavones are produced almost exclusively by the members of the bean family, Fabaceae (Leguminosae ...
s also produce non-hormonal effects.
Molecular function
Genistein influences multiple
biochemical
Biochemistry or biological chemistry is the study of chemical processes within and relating to living organisms. A sub-discipline of both chemistry and biology, biochemistry may be divided into three fields: structural biology, enzymology an ...
functions in living cells:
*
full agonist
An agonist is a chemical that activates a receptor to produce a biological response. Receptors are cellular proteins whose activation causes the cell to modify what it is currently doing. In contrast, an antagonist blocks the action of the ago ...
of
ERβ
Estrogen receptor beta (ERβ) also known as NR3A2 (nuclear receptor subfamily 3, group A, member 2) is one of two main types of estrogen receptor—a nuclear receptor which is activated by the sex hormone estrogen. In humans ERβ is encoded by ...
(
EC50 = 7.62 nM) and, to a much lesser extent (~20-fold),
full agonist
An agonist is a chemical that activates a receptor to produce a biological response. Receptors are cellular proteins whose activation causes the cell to modify what it is currently doing. In contrast, an antagonist blocks the action of the ago ...
or
partial agonist
In pharmacology, partial agonists are drugs that bind to and activate a given receptor, but have only partial efficacy at the receptor relative to a full agonist. They may also be considered ligands which display both agonistic and antagonistic e ...
of
ERα
Estrogen receptor alpha (ERα), also known as NR3A1 (nuclear receptor subfamily 3, group A, member 1), is one of two main types of estrogen receptor, a nuclear receptor (mainly found as a chromatin-binding protein)
that is activated by the sex ...
* agonist of
G protein-coupled estrogen receptor
G protein-coupled estrogen receptor 1 (GPER), also known as G protein-coupled receptor 30 (GPR30), is a protein that in humans is encoded by the ''GPER'' gene. GPER binds to and is activated by the female sex hormone estradiol and is responsible ...
(affinity of 133 nM)
* activation of peroxisome proliferator-activated receptors (
PPAR
In the field of molecular biology, the peroxisome proliferator-activated receptors (PPARs) are a group of nuclear receptor proteins that function as transcription factors regulating the expression of genes. PPARs play essential roles in the reg ...
s)
* inhibition of several
tyrosine kinase
A tyrosine kinase is an enzyme that can transfer a phosphate group from ATP to the tyrosine residues of specific proteins inside a cell. It functions as an "on" or "off" switch in many cellular functions.
Tyrosine kinases belong to a larger cla ...
s
* inhibition of
topoisomerase
DNA topoisomerases (or topoisomerases) are enzymes that catalyze changes in the topological state of DNA, interconverting relaxed and supercoiled forms, linked (catenated) and unlinked species, and knotted and unknotted DNA. Topological issues i ...
* inhibition of
AAAD
* direct antioxidation with some pro oxidative features
* activation of
Nrf2
Nuclear factor erythroid 2-related factor 2 (NRF2), also known as nuclear factor erythroid-derived 2-like 2, is a transcription factor that in humans is encoded by the ''NFE2L2'' gene. NRF2 is a basic leucine zipper (bZIP) protein that may reg ...
antioxidative response
* stimulation of
autophagy
Autophagy (or autophagocytosis; from the Ancient Greek , , meaning "self-devouring" and , , meaning "hollow") is the natural, conserved degradation of the cell that removes unnecessary or dysfunctional components through a lysosome-dependent re ...
* inhibition of the mammalian
hexose
In chemistry, a hexose is a monosaccharide (simple sugar) with six carbon atoms. The chemical formula for all hexoses is C6H12O6, and their molecular weight is 180.156 g/mol.
Hexoses exist in two forms, open-chain or cyclic, that easily convert ...
transporter
GLUT1
Glucose transporter 1 (or GLUT1), also known as solute carrier family 2, facilitated glucose transporter member 1 (SLC2A1), is a uniporter protein that in humans is encoded by the ''SLC2A1'' gene. GLUT1 facilitates the transport of glucose across ...
* contraction of several types of
smooth muscle
Smooth muscle is an involuntary non-striated muscle, so-called because it has no sarcomeres and therefore no striations (''bands'' or ''stripes''). It is divided into two subgroups, single-unit and multiunit smooth muscle. Within single-unit mus ...
s
* modulation of CFTR channel, potentiating its opening at low concentration and inhibiting it a higher doses.
* inhibition of cytosine methylation
* inhibition of
DNA methyltransferase
In biochemistry, the DNA methyltransferase (DNA MTase, DNMT) family of enzymes catalyze the transfer of a methyl group to DNA. DNA methylation serves a wide variety of biological functions. All the known DNA methyltransferases use S-adenosyl m ...
* inhibition of the
glycine receptor
The glycine receptor (abbreviated as GlyR or GLR) is the receptor of the amino acid neurotransmitter glycine. GlyR is an ionotropic receptor that produces its effects through chloride current. It is one of the most widely distributed inhibitory ...
* inhibition of the
nicotinic acetylcholine receptor
Nicotinic acetylcholine receptors, or nAChRs, are receptor polypeptides that respond to the neurotransmitter acetylcholine. Nicotinic receptors also respond to drugs such as the agonist nicotine. They are found in the central and peripheral ne ...
Activation of PPARs
Isoflavones genistein and daidzein bind to and transactivate all three PPAR isoforms, α, δ, and γ.
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. 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.
[
]
Tyrosine kinase inhibitor
The main known activity of genistein is tyrosine kinase inhibitor
A tyrosine kinase inhibitor (TKI) is a pharmaceutical drug that inhibits tyrosine kinases. Tyrosine kinases are enzymes responsible for the activation of many proteins by signal transduction cascades. The proteins are activated by adding a phosph ...
, mostly of epidermal growth factor receptor
The epidermal growth factor receptor (EGFR; ErbB-1; HER1 in humans) is a transmembrane protein that is a receptor for members of the epidermal growth factor family (EGF family) of extracellular protein ligands.
The epidermal growth factor recept ...
(EGFR). Tyrosine kinases are less widespread than their ser/thr counterparts but implicated in almost all cell growth and proliferation signal cascades.
Redox-active—not only antioxidant
Genistein may act as direct antioxidant
Antioxidants are compounds that inhibit oxidation, a chemical reaction that can produce free radicals. This can lead to polymerization and other chain reactions. They are frequently added to industrial products, such as fuels and lubricant ...
, similar to many other isoflavone Isoflavones are substituted derivatives of isoflavone, a type of naturally occurring isoflavonoids, many of which act as phytoestrogens in mammals. Isoflavones are produced almost exclusively by the members of the bean family, Fabaceae (Leguminosae ...
s, and thus may alleviate damaging effects of free radicals
In chemistry, a radical, also known as a free radical, is an atom, molecule, or ion that has at least one unpaired valence electron.
With some exceptions, these unpaired electrons make radicals highly chemically reactive. Many radicals spont ...
in tissues.
The same molecule of genistein, similar to many other isoflavone Isoflavones are substituted derivatives of isoflavone, a type of naturally occurring isoflavonoids, many of which act as phytoestrogens in mammals. Isoflavones are produced almost exclusively by the members of the bean family, Fabaceae (Leguminosae ...
s, by generation of free radicals poison topoisomerase
DNA topoisomerases (or topoisomerases) are enzymes that catalyze changes in the topological state of DNA, interconverting relaxed and supercoiled forms, linked (catenated) and unlinked species, and knotted and unknotted DNA. Topological issues i ...
II, an enzyme important for maintaining DNA stability.[
]
Human cells turn on beneficial, detoxifying Nrf2
Nuclear factor erythroid 2-related factor 2 (NRF2), also known as nuclear factor erythroid-derived 2-like 2, is a transcription factor that in humans is encoded by the ''NFE2L2'' gene. NRF2 is a basic leucine zipper (bZIP) protein that may reg ...
factor in response to genistein insult. This pathway may be responsible for observed health maintaining properties of small doses of genistein.
Anthelmintic
The root-tuber peel extract of the leguminous plant '' Felmingia vestita'' is the traditional anthelmintic
Anthelmintics or antihelminthics are a group of antiparasitic drugs that expel parasitic worms (helminths) and other internal parasites from the body by either stunning or killing them and without causing significant damage to the host. They may a ...
of the Khasi tribes of India. While investigating its anthelmintic activity, genistein was found to be the major isoflavone Isoflavones are substituted derivatives of isoflavone, a type of naturally occurring isoflavonoids, many of which act as phytoestrogens in mammals. Isoflavones are produced almost exclusively by the members of the bean family, Fabaceae (Leguminosae ...
responsible for the deworming
Deworming (sometimes known as worming, drenching or dehelmintization) is the giving of an anthelmintic drug (a wormer, dewormer, or drench) to a human or animals to rid them of helminths parasites, such as roundworm, flukes and tapeworm. Purg ...
property. Genistein was subsequently demonstrated to be highly effective against intestinal parasite
An intestinal parasite infection is a condition in which a parasite infects the gastro-intestinal tract of humans and other animals. Such parasites can live anywhere in the body, but most prefer the intestinal wall.
Routes of exposure and infe ...
s such as the poultry
Poultry () are domesticated birds kept by humans for their eggs, their meat or their feathers. These birds are most typically members of the superorder Galloanserae (fowl), especially the order Galliformes (which includes chickens, quails, a ...
cestode '' Raillietina echinobothrida'', the pork
Pork is the culinary name for the meat of the domestic pig (''Sus domesticus''). It is the most commonly consumed meat worldwide, with evidence of pig husbandry dating back to 5000 BCE.
Pork is eaten both freshly cooked and preserved; ...
trematode
Trematoda is a class of flatworms known as flukes. They are obligate internal parasites with a complex life cycle requiring at least two hosts. The intermediate host, in which asexual reproduction occurs, is usually a snail. The definitive host ...
'' Fasciolopsis buski
''Fasciolopsis'' () is a genus of trematodes. They are also known as giant intestinal flukes.
Only one species is recognised: ''Fasciolopsis buski''. It is a notable parasite of medical importance in humans and veterinary importance in pigs. I ...
'', and the sheep liver fluke ''Fasciola hepatica''. It exerts its anthelmintic activity by inhibiting the enzymes of glycolysis
Glycolysis is the metabolic pathway that converts glucose () into pyruvate (). The free energy released in this process is used to form the high-energy molecules adenosine triphosphate (ATP) and reduced nicotinamide adenine dinucleotide (NADH ...
and glycogenolysis, and disturbing the Ca2+ homeostasis and NO activity in the parasites
Parasitism is a Symbiosis, close relationship between species, where one organism, the parasite, lives on or inside another organism, the Host (biology), host, causing it some harm, and is Adaptation, adapted structurally to this way of lif ...
. It has also been investigated in human tapeworms such as ''Echinococcus multilocularis
''Echinococcus multilocularis'' is a small cyclophyllid tapeworm found extensively in the northern hemisphere. ''E. multilocularis,'' along with other members of the ''Echinococcus'' genus (especially '' E. granulosus''), produce diseases known ...
'' and '' E. granulosus'' metacestodes that genistein and its derivatives, Rm6423 and Rm6426, are potent cestocides.
Atherosclerosis
Genistein protects against pro-inflammatory factor-induced vascular endothelial barrier dysfunction and inhibits leukocyte
White blood cells, also called leukocytes or leucocytes, are the cells of the immune system that are involved in protecting the body against both infectious disease and foreign invaders. All white blood cells are produced and derived from mult ...
-endothelium
The endothelium is a single layer of squamous endothelial cells that line the interior surface of blood vessels and lymphatic vessels. The endothelium forms an interface between circulating blood or lymph in the lumen and the rest of the vessel ...
interaction, thereby modulating vascular inflammation, a major event in the pathogenesis
Pathogenesis is the process by which a disease or disorder develops. It can include factors which contribute not only to the onset of the disease or disorder, but also to its progression and maintenance. The word comes from Greek πάθος ''pat ...
of atherosclerosis
Atherosclerosis is a pattern of the disease arteriosclerosis in which the wall of the artery develops abnormalities, called lesions. These lesions may lead to narrowing due to the buildup of atheroma, atheromatous plaque. At onset there are usu ...
.
Cancer links
Genistein and other isoflavone Isoflavones are substituted derivatives of isoflavone, a type of naturally occurring isoflavonoids, many of which act as phytoestrogens in mammals. Isoflavones are produced almost exclusively by the members of the bean family, Fabaceae (Leguminosae ...
s have been identified as angiogenesis inhibitors An angiogenesis inhibitor is a substance that inhibits the growth of new blood vessels ( angiogenesis). Some angiogenesis inhibitors are endogenous and a normal part of the body's control and others are obtained exogenously through pharmaceutical d ...
, and found to inhibit the uncontrolled cell growth of cancer
Cancer is a group of diseases involving abnormal cell growth with the potential to invade or spread to other parts of the body. These contrast with benign tumors, which do not spread. Possible signs and symptoms include a lump, abnormal b ...
, most likely by inhibiting the activity of substances in the body that regulate cell division
Cell division is the process by which a parent cell (biology), cell divides into two daughter cells. Cell division usually occurs as part of a larger cell cycle in which the cell grows and replicates its chromosome(s) before dividing. In eukar ...
and cell survival (growth factors
A growth factor is a naturally occurring substance capable of stimulating cell proliferation, wound healing, and occasionally cellular differentiation. Usually it is a secreted protein or a steroid hormone. Growth factors are important for regu ...
). Various studies have found that moderate doses of genistein have inhibitory effects on cancer
Cancer is a group of diseases involving abnormal cell growth with the potential to invade or spread to other parts of the body. These contrast with benign tumors, which do not spread. Possible signs and symptoms include a lump, abnormal b ...
s of the prostate
The prostate is both an Male accessory gland, accessory gland of the male reproductive system and a muscle-driven mechanical switch between urination and ejaculation. It is found only in some mammals. It differs between species anatomically, ...
, cervix
The cervix or cervix uteri (Latin, 'neck of the uterus') is the lower part of the uterus (womb) in the human female reproductive system. The cervix is usually 2 to 3 cm long (~1 inch) and roughly cylindrical in shape, which changes during ...
, brain
A brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. It is located in the head, usually close to the sensory organs for senses such as vision. It is the most complex organ in a v ...
, breast
The breast is one of two prominences located on the upper ventral region of a primate's torso. Both females and males develop breasts from the same embryological tissues.
In females, it serves as the mammary gland, which produces and secret ...
[ and colon.] It has also been shown that genistein makes some cells more sensitive to radio-therapy.; although, timing of phytoestrogen
A phytoestrogen is a plant-derived xenoestrogen (see estrogen) not generated within the endocrine system, but consumed by eating plants or manufactured foods. Also called a "dietary estrogen", it is a diverse group of naturally occurring nonstero ...
use is also important.
Genistein's chief method of activity is as a tyrosine kinase inhibitor
A tyrosine kinase inhibitor (TKI) is a pharmaceutical drug that inhibits tyrosine kinases. Tyrosine kinases are enzymes responsible for the activation of many proteins by signal transduction cascades. The proteins are activated by adding a phosph ...
. 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. 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 Isoflavones are substituted derivatives of isoflavone, a type of naturally occurring isoflavonoids, many of which act as phytoestrogens in mammals. Isoflavones are produced almost exclusively by the members of the bean family, Fabaceae (Leguminosae ...
may be potential immunosuppressant
Immunosuppressive drugs, also known as immunosuppressive agents, immunosuppressants and antirejection medications, are drugs that inhibit or prevent activity of the immune system.
Classification
Immunosuppressive drugs can be classified in ...
. Genistein has been used to selectively target pre B-cells via conjugation with an anti-CD19 antibody.
Studies on rodents have found genistein to be useful in the treatment of leukemia
Leukemia ( also spelled leukaemia and pronounced ) is a group of blood cancers that usually begin in the bone marrow and result in high numbers of abnormal blood cells. These blood cells are not fully developed and are called ''blasts'' or ' ...
, and that it can be used in combination with certain other antileukemic drugs to improve their efficacy.
Estrogen receptor — more cancer links
Due to its structure similarity to 17β-estradiol (estrogen
Estrogen or oestrogen is a category of sex hormone responsible for the development and regulation of the female reproductive system and secondary sex characteristics. There are three major endogenous estrogens that have estrogenic hormonal acti ...
), genistein can compete with it and bind to estrogen receptor
Estrogen receptors (ERs) are a group of proteins found inside cells. They are receptors that are activated by the hormone estrogen ( 17β-estradiol). Two classes of ER exist: nuclear estrogen receptors (ERα and ERβ), which are members of the ...
s. However, genistein shows much higher affinity toward estrogen receptor β than toward estrogen receptor α
Estrogen receptor alpha (ERα), also known as NR3A1 (nuclear receptor subfamily 3, group A, member 1), is one of two main types of estrogen receptor, a nuclear receptor (mainly found as a chromatin-binding protein)
that is activated by the sex ...
.
Data from ''in vitro
''In vitro'' (meaning in glass, or ''in the glass'') studies are performed with microorganisms, cells, or biological molecules outside their normal biological context. Colloquially called "test-tube experiments", these studies in biology an ...
'' and ''in vivo
Studies that are ''in vivo'' (Latin for "within the living"; often not italicized in English) are those in which the effects of various biological entities are tested on whole, living organisms or cells, usually animals, including humans, and ...
'' 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. It was also found to decrease efficiency of tamoxifen
Tamoxifen, sold under the brand name Nolvadex among others, is a selective estrogen receptor modulator used to prevent breast cancer in women and treat breast cancer in women and men. It is also being studied for other types of cancer. It has b ...
and letrozole
Letrozole, sold under the brand name Femara among others, is an aromatase inhibitor medication that is used in the treatment of breast cancer.
It was patented in 1986 and approved for medical use in 1996. In 2020, it was the 257th most common ...
- drugs commonly used in breast cancer therapy. Genistein was found to inhibit immune response towards cancer cells allowing their survival.
Effects in males
Isoflavones can act like estrogen
Estrogen or oestrogen is a category of sex hormone responsible for the development and regulation of the female reproductive system and secondary sex characteristics. There are three major endogenous estrogens that have estrogenic hormonal acti ...
, 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
Apoptosis (from grc, ἀπόπτωσις, apóptōsis, 'falling off') is a form of programmed cell death that occurs in multicellular organisms. Biochemical events lead to characteristic cell changes (morphology) and death. These changes incl ...
of testicular cells at certain levels, thus raising concerns about effects it could have on male fertility; 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.
Carcinogenic and toxic potential
Genistein was, among other flavonoid
Flavonoids (or bioflavonoids; from the Latin word ''flavus'', meaning yellow, their color in nature) are a class of polyphenolic secondary metabolites found in plants, and thus commonly consumed in the diets of humans.
Chemically, flavonoids ...
s, found to be a strong topoisomerase inhibitor
Topoisomerase inhibitors are chemical compounds that block the action of topoisomerases, which are broken into two broad subtypes: type I topoisomerases (TopI) and type II topoisomerases (TopII). Topoisomerase plays important roles in cellular rep ...
, similarly to some chemotherapeutic anticancer drugs ex. etoposide
Etoposide, sold under the brand name Vepesid among others, is a chemotherapy medication used for the treatments of a number of types of cancer including testicular cancer, lung cancer, lymphoma, leukemia, neuroblastoma, and ovarian cancer. It is ...
and doxorubicin
Doxorubicin, sold under the brand name Adriamycin among others, is a chemotherapy medication used to treat cancer. This includes breast cancer, bladder cancer, Kaposi's sarcoma, lymphoma, and acute lymphocytic leukemia. It is often used togeth ...
. In high doses it was found to be strongly toxic to normal cells. This effect may be responsible for both anticarcinogenic and carcinogenic potential of the substance. It was found to deteriorate DNA of cultured blood stem cells, which may lead to leukemia. Genistein among other flavonoid
Flavonoids (or bioflavonoids; from the Latin word ''flavus'', meaning yellow, their color in nature) are a class of polyphenolic secondary metabolites found in plants, and thus commonly consumed in the diets of humans.
Chemically, flavonoids ...
s is suspected to increase risk of infant leukemia when consumed during pregnancy.
Sanfilippo syndrome treatment
Genistein decreases pathological accumulation of glycosaminoglycan
Glycosaminoglycans (GAGs) or mucopolysaccharides are long, linear polysaccharides consisting of repeating disaccharide units (i.e. two-sugar units). The repeating two-sugar unit consists of a uronic sugar and an amino sugar, except in the case ...
s in Sanfilippo syndrome
Sanfilippo syndrome, also known as mucopolysaccharidosis type III (MPS III), is a rare autosomal recessive lysosomal storage disease that primarily affects the brain and spinal cord. It is caused by a buildup of large sugar molecules called g ...
. ''In vitro'' animal studies and clinical experiments suggest that the symptoms of the disease may be alleviated by adequate dose of genistein. Genistein was found to also possess toxic properties toward brain cells. Among many pathways stimulated by genistein, autophagy
Autophagy (or autophagocytosis; from the Ancient Greek , , meaning "self-devouring" and , , meaning "hollow") is the natural, conserved degradation of the cell that removes unnecessary or dysfunctional components through a lysosome-dependent re ...
may explain the observed efficiency of the substance as autophagy
Autophagy (or autophagocytosis; from the Ancient Greek , , meaning "self-devouring" and , , meaning "hollow") is the natural, conserved degradation of the cell that removes unnecessary or dysfunctional components through a lysosome-dependent re ...
is significantly impaired in the disease.
Cognition
A study looking at Italians older than 50 found that those with the highest genistein intake had the lowest odds of cognitive impairment.
Related compounds
* Genistin
Genistin is an isoflavone found in a number of dietary plants like soy and kudzu. It was first isolated in 1931 from the 90% methanol extract of a soybean meal, when it was found that hydrolysis with hydrochloric acid produced 1 mole each of geni ...
is the 7-O-beta-D-glucoside
A glucoside is a glycoside that is derived from glucose. Glucosides are common in plants, but rare in animals. Glucose is produced when a glucoside is hydrolysed by purely chemical means, or decomposed by fermentation or enzymes.
The name was o ...
of genistein.
* Wighteone
Wighteone is an isoflavone Isoflavones are substituted derivatives of isoflavone, a type of naturally occurring isoflavonoids, many of which act as phytoestrogens in mammals. Isoflavones are produced almost exclusively by the members of the bean f ...
can be described as 6- isopentenyl genistein
* KBU2046 under investigation for prostate cancer
Prostate cancer is cancer of the prostate. Prostate cancer is the second most common cancerous tumor worldwide and is the fifth leading cause of cancer-related mortality among men. The prostate is a gland in the male reproductive system that sur ...
.
* B43-genistein, an anti- CD19 antibody linked to genistein e.g. for leukemia
Leukemia ( also spelled leukaemia and pronounced ) is a group of blood cancers that usually begin in the bone marrow and result in high numbers of abnormal blood cells. These blood cells are not fully developed and are called ''blasts'' or ' ...
.
See also
* (S)-Equol
* Liquiritigenin
Liquiritigenin is a flavanone that was isolated from ''Glycyrrhiza uralensis'', and is found in a variety of plants, including ''Glycyrrhiza glabra'' (licorice). It is an estrogenic compound which acts as a selective agonist of the ERβ subtype ...
* Menerba Menerba, also known as Menopause Formula 101 (MF-101), is a botanical drug candidate that acts as a selective estrogen receptor modulator (SERM) which is being studied for its potential to relieve hot flashes associated with menopause. Menerba, an ...
References
External links
Compound Summary at NCBI PubChem
Fact Sheet at Zerobreastcancer
Information at Phytochemicals
Description at NCI Drug Dictionary
{{Navboxes
, title = Pharmacodynamics
Pharmacodynamics (PD) is the study of the biochemical and physiologic effects of drugs (especially pharmaceutical drugs). The effects can include those manifested within animals (including humans), microorganisms, or combinations of organisms (fo ...
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, list1 =
{{Cannabinoid receptor modulators
{{Estrogen receptor modulators
{{Estrogen-related receptor modulators
{{Glycine receptor modulators
{{Monoamine metabolism modulators
{{PPAR modulators
{{Thyroid hormone receptor modulators
3α-Hydroxysteroid dehydrogenase inhibitors
21-Hydroxylase inhibitors
Dietary supplements
Flavonoid antioxidants
GPER agonists
Isoflavones
Nutrients
Protein kinase inhibitors
Phytoestrogens
Glycine receptor antagonists
Selective ERβ agonists
Steroid sulfotransferase inhibitors