Genistein

Names

[ CAS No. ]:
446-72-0

[ Name ]:
Genistein

[Synonym ]:
5-18-04-00594 (Beilstein Handbook Reference)
5,7,4'-trihydroxyisoflavone
4',5,7-trihydroxyisoflavone
Genistein
GeniVida
4H-1-Benzopyran-4-one, 5,7-dihydroxy-3-(4-hydroxyphenyl)-
prunetol
EINECS 207-174-9
genisteol
Bonistein
NPI 031L
MFCD00016952
5,7-Dihydroxy-3-(4-hydroxyphenyl)-4H-chromen-4-one
5,7-Dihydroxy-3-(4-hydroxyphenyl)-4H-1-benzopyran-4-one
Genestein
sophoricol
GLYCITEN

Biological Activity

[Description]:

Genistein, a soy isoflavone, is a multiple tyrosine kinases inhibitor which acts as a chemotherapeutic agent against different types of cancer, mainly by altering apoptosis, the cell cycle, and angiogenesis and inhibiting metastasis.

[Related Catalog]:

Signaling Pathways >> Autophagy >> Autophagy

Signaling Pathways >> JAK/STAT Signaling >> EGFR

Signaling Pathways >> Protein Tyrosine Kinase/RTK >> EGFR

Natural Products >> Flavonoids

Research Areas >> Cancer

[Target]

EGFR:0.6 μM (IC50, Cell Assay)

[In Vitro]

Genistein inhibits serum-stimulated growth of MCF-7 and T47D ER+ cells with IC50 values of 7.6 and 8.7 μg/mL by dye exclusion, respectively, and 8.7 and 10.6 μg/mL by [3H]thymidmne incorporation, respectively. These values are similar to the IC50 values of 9.4 and 7 μg/mL for MCF-7 and T47D ER+ cells, respectively, obtained with the MTT assay. Additionally, Genistein at concentrations up to 20 μg/mL does not alter MTT mitochondrial reduction when compared to control cells in an 8 h incubation period. Furthermore, neither biochanin A or daidzein are found to interfere with the MTT assay at IC50 concentrations. Therefore, the MTT assay is valid for determining growth inhibition by Genistein at concentrations under 20 μg/mL in the systems studied[1].

[In Vivo]

In the present study, the effective dose of morphine caused a significant decrease in testis weight of mice compared to Saline group (p=0.00). Moreover, testis weight are significantly increase in treated animals with Genistein and Genistein plus morphine in all doses in comparison with morphine group (p=0.028). Morphine caused a significant decrease in the testosterone, LH and FSH hormones compared to saline group (p=0.00). In addition, the testosterone, LH and FSH hormones increased significantly in Genistein (p<0.05) and Genistein plus morphine in all groups administration compared to morphine group (p=0.024)[2]. Bisphenol A (BPA) treatment alone and combined with Genistein had no significant effect on the protein expression of LC3II and PPARα in liver of STD- or HFD-fed rats (P>0.05; P>0.05). Significant decreasing of the protein expression of PPARγ in liver is observed when Genistein is added to rats, compared to either HFD group or HFD-BPA group[3].

[Cell Assay]

The IC50 values for Genistein are determined by the MTT assay. Briefly, the MTT assay is a colorimetric assay that is based on the ability of living but not dead cells to reduce a tetrazolium-based compound to a blue formazan product. The formazan crystals are solubilized in DMSO, and the absorbance is measured at 540 nm. The absorbance at 540 nm is proportional to the number of viable cells. The lC50 values obtained with the MTT assay are compared with the lC50 values obtained by counting viable cells using trypan blue dye exclusion and by tritiated thymidine incorporation into DNA[1].

[Animal admin]

Mice[2] Balb/c male mice are used. Genistein is administered as follows: On days 1-30, Genistein once daily, interaperitoneally injecting. Morphine plus Genistein is administered as follows: On days 1-30, Genistein once daily plus morphine, interaperitoneally injecting (17, 18). The same volume of saline is administered. Mice are randomly divided into 8 groups (n=6). 1) Normal saline group (1 mL DW/daily); 2) Morphine treated group; 3) Genistein 1 mg/kg treated group; 4) Genistein 2 mg/kg treated group 5) Genistein 4 mg/kg treated group; 6) Morphine plus Genistein 1 mg/kg treated group; 7) Morphine plus Genistein 2 mg/kg treated group; 8) Morphine plus Genistein 4 mg/kg treated group. Rats[3] Male 8-week-old Wistar rats (150-180g) are used. After one week acclimation, all rats are randomly divided into 8 groups with 10 rats per group and treated for 35 weeks as follows: (1) STD group is fed with rodent standard chow diet (STD); (2) STD-BPA group is fed with STD and administered with BPA (50 μg/kg/day); (3) STD-(BPA+G) group is fed with STD and administered with BPA (50 μg/kg/day) plus Genistein (10 mg/kg/day); (4) STD-G group is fed with STD and administered with Genistein (10 mg/kg/day); (5) HFD group received high-fat diet (HFD); (6) HFD-BPA group is fed with HFD and administered with BPA (50 μg/kg/day); (7) STD-(BPA+G) group is fed with HFD and administered with BPA (50 μg/kg/day) plus Genistein (10 mg/kg/day); (8) HFD-G group is fed with HFD and administrated with Genistein (10 mg/kg/day). All the male genitors are treated for 35 weeks consecutively. The details of BPA (50 μg/kg/day) and Genistein (10 mg/kg/day) treatment methods have been described previously: BPA is dissolved in corn oil and diluted with three stock solutions (20, 40, 80, and 120 μg/mL).

[References]

[1]. Peterson G, et al. Genistein inhibits both estrogen and growth factor-stimulated proliferation of human breast cancer cells. Cell Growth Differ. 1996 Oct;7(10):1345-51.

[2]. Jalili C, et al. Effect of Genistein on reproductive parameter and serum nitric oxide levels in morphine-treated mice. Int J Reprod Biomed (Yazd). 2016 Feb;14(2):95-102.

[3]. Ding S, et al. Environmentally Relevant Dose of Bisphenol A Does Not Affect Lipid Metabolism and Has No Synergetic or Antagonistic Effects on Genistein's Beneficial Roles on Lipid Metabolism. PLoS One. 2016 May 12;11(5):e0155352.

[Related Small Molecules]

Chemical & Physical Properties

[ Density]:
1.5±0.1 g/cm3

[ Boiling Point ]:
555.5±50.0 °C at 760 mmHg

[ Melting Point ]:
297-298 °C

[ Molecular Formula ]:
C₁₅H₁₀O₅

[ Molecular Weight ]:
270.237

[ Flash Point ]:
217.1±23.6 °C

[ Exact Mass ]:
270.052826

[ PSA ]:
90.90000

[ LogP ]:
2.96

[ Vapour Pressure ]:
0.0±1.6 mmHg at 25°C

[ Index of Refraction ]:
1.732

[ Storage condition ]:
−20°C

[ Stability ]:
Light Sensitive

[ Water Solubility ]:
insoluble

MSDS

Click to get detail MSDS

Toxicological Information

CHEMICAL IDENTIFICATION

RTECS NUMBER :: NR2392000

CHEMICAL NAME :: Isoflavone, 4',5,7-trihydroxy-

CAS REGISTRY NUMBER :: 446-72-0

BEILSTEIN REFERENCE NO. :: 0263823

LAST UPDATED :: 199801

DATA ITEMS CITED :: 12

MOLECULAR FORMULA :: C15-H10-O5

MOLECULAR WEIGHT :: 270.25

WISWESSER LINE NOTATION :: T66 BO EVT&J CR DQ& IQ

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

TYPE OF TEST :: LD - Lethal dose

ROUTE OF EXPOSURE :: Intraperitoneal

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: >500 mg/kg

TOXIC EFFECTS :: Details of toxic effects not reported other than lethal dose value

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Subcutaneous

DOSE :: 125 mg/kg

SEX/DURATION :: female 16-20 day(s) after conception

TOXIC EFFECTS :: Reproductive - Specific Developmental Abnormalities - urogenital system

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Subcutaneous

DOSE :: 625 mg/kg

SEX/DURATION :: female 16-20 day(s) after conception

TOXIC EFFECTS :: Reproductive - Effects on Newborn - growth statistics (e.g.%, reduced weight gain)

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 1680 mg/kg

SEX/DURATION :: female 21 day(s) pre-mating

TOXIC EFFECTS :: Reproductive - Maternal Effects - other effects

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 13200 mg/kg

SEX/DURATION :: male 22 day(s) pre-mating

TOXIC EFFECTS :: Reproductive - Fertility - male fertility index (e.g. # males impregnating females per # males exposed to fertile nonpregnant females)

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 18600 mg/kg

SEX/DURATION :: female 31 day(s) pre-mating

TOXIC EFFECTS :: Reproductive - Effects on Newborn - stillbirth

MUTATION DATA

TYPE OF TEST :: Mutation in mammalian somatic cells

TEST SYSTEM :: Rodent - hamster Lung

DOSE/DURATION :: 25 umol/L

REFERENCE :: FCTOD7 Food and Chemical Toxicology. (Pergamon Press Inc., Maxwell House, Fairview Park, Elmsford, NY 10523) V.20- 1982- Volume(issue)/page/year: 35,605,1997

Safety Information

[ Symbol ]:

GHS07

[ Signal Word ]:
Warning

[ Hazard Statements ]:
H302

[ Precautionary Statements ]:
P301 + P312 + P330

[ Personal Protective Equipment ]:
Eyeshields;Faceshields;Gloves;type N95 (US);type P1 (EN143) respirator filter

[ Hazard Codes ]:
Xi: Irritant;

[ Risk Phrases ]:
R36/38

[ Safety Phrases ]:
S26-S24/25-S22

[ RIDADR ]:
NONH for all modes of transport

[ WGK Germany ]:
3

[ RTECS ]:
NR2392000

[ HS Code ]:
2932999099

Synthetic Route

Click to get detail synthetic route

Precursor & DownStream

Precursor

DownStream

Customs

[ HS Code ]: 2932999099

[ Summary ]:
2932999099. other heterocyclic compounds with oxygen hetero-atom(s) only. VAT:17.0%. Tax rebate rate:13.0%. . MFN tariff:6.5%. General tariff:20.0%

Articles

Neuropilin 1 is an entry factor that promotes EBV infection of nasopharyngeal epithelial cells.

Nat. Commun. 6 , 6240, (2015)

Epstein-Barr virus (EBV) is implicated as an aetiological factor in B lymphomas and nasopharyngeal carcinoma. The mechanisms of cell-free EBV infection of nasopharyngeal epithelial cells remain elusiv...

A precisely substituted benzopyran targets androgen refractory prostate cancer cells through selective modulation of estrogen receptors.

Toxicol. Appl. Pharmacol. 283(3) , 187-97, (2015)

Dietary consumption of phytoestrogens like genistein has been linked with lower incidence of prostate cancer. The estradiol-like benzopyran core of genistein confers estrogen receptor-β (ER-β) selecti...

Direct cellular delivery of human proteasomes to delay tau aggregation.

Nat. Commun. 5 , 5633, (2014)

The 26S proteasome is the primary machinery that degrades ubiquitin (Ub)-conjugated proteins, including many proteotoxic proteins implicated in neurodegeneraton. It has been suggested that the elevati...