| Properties | Information | |
|---|---|---|
| PhytoCAT-ID | PhytoCAT-640 | |
| Phytochemical name or plant extracts | Genistein | |
| PMID | 10945618 | |
| Literature evidence | Soybeans contain a significant amount of the isoflavones daidzein and genistein, which are weak estrogens. | |
| IUPAC name | 5,7-dihydroxy-3-(4-hydroxyphenyl)chromen-4-one | |
| Phytochemicals’ class or type of plant extracts | Flavonoid | |
| Source of phytochemicals or plant Extracts | Genista tinctoria | |
| Geographical availability | Afghanistan, Albania, Altay, Austria, Baltic States, Belarus, Belgium, Bulgaria, Central European Rus, Czechoslovakia, Denmark, East European Russia, France, Germany, Great Britain, Greece, Hungary, Iran, Italy, Kazakhstan, Krym, Lebanon-Syria, Netherlands, North Caucasus, Northwest European R, Norway, Poland, Romania, South European Russi, Spain, Sweden, Switzerland, Transcaucasus, Turkey, Turkey-in-Europe, Ukraine, West Siberia, Yugoslavia | |
| Plant parts | Seeds | |
| Other cancers | Breast cancer, Neurobastoma | |
| Target gene or protein | miR-155, BRCA1 , PI3K/AKT, CDK2, Cyclin D1, VEGF, MMP2, MMP9, uPA, Cyclin B1, mir-23b, NF-κB, p53, Chk2, GPR30-Akt, pRb105, FOXO3, PTEN, casein kinase, p27, UPR, GRP78, IRE1α, ATF4, Beclin-1, TGFβ, Foxp3, CD8a, PI, PIPK, Aromatase, ATRX, SUV39H1/H2, HP1BP3, KLf4, hTERT, CDK1, ER-beta, BRCA1, TNF, BARD1, p53, pS2, jun, BAX, BAP1, BARD1, BRCA2 | |
| Gene or Protein evidence | In parallel with reduced cell viability, miR-155 is downregulated, whereas proapoptotic and anticell proliferative miR-155 targets FOXO3, PTEN, casein kinase, and p27 are upregulated in MDA-MB-435 and Hs578t cells in response to genistein treatment. Epigenetic Activation of BRCA1 by Genistein In Vivo and Triple Negative Breast Cancer Cells Linked to Antagonism toward Aryl Hydrocarbon Receptor. Genistein Inhibits Proliferation of BRCA1 Mutated Breast Cancer Cells: The GPR30-Akt Axis as a Potential Target. Genistein potentiates Centchroman induced antineoplasticity in breast cancer via PI3K/Akt deactivation and ROS dependent induction of apoptosis. Genistein and the fungal toxin zearalenone were found to increase the activity of cyclin dependent kinase 2 (Cdk2) and cyclin D1 synthesis and stimulate the hyperphosphorylation of the retinoblastoma susceptibility gene product pRb105 in MCF-7 cells. Genistein could inhibit expression of angiogenesis-related factors VEGF, MMP-2,9 and uPA in HER-2/neu-overexpressing breast cancer cells, and this may be part of molecular mechanism of its anti-angiogenesis in HER-2/neu-overexpressing breast cancer. Genistein induces G2/M phase arrest by down-regulating cyclin B1 expression, which is attributable to its suppression of GPR30 activation and Akt phosphorylation in BRCA1 impaired breast cancer cells. Genistein-induced mir-23b expression inhibits the growth of breast cancer cells. From these results, we conclude that the inactivation of NF-kappaB by genistein in MDA-MB-231 breast cancer cells is partly mediated via Akt pathway, which could be useful for rational design of strategies for the prevention and/or treatment of breast cancer. Together our data suggest that ATM is required for activation of a DNA damage-induced pathway that activates p53 and Chk2 in response to genistein. We observed downregulation of unfolded protein response (UPR) and autophagy related genes (GRP78, IRE1α, ATF4 and Beclin-1), and genes linked to immunosuppression (TGFβ and Foxp3), and upregulation of cytotoxic T cell marker CD8a in the tumors of the lifetime GEN group, compared with controls, post-diagnosis, and/or adult GEN groups. Quercetin and genistein are able to inhibit PI and PIP kinase activities and reduce IP3 concentration in vivo and in tissue culture systems. Polyphenolic natural products and natural product-inspired steroidal mimics as aromatase inhibitors. Prolonged phytochemical exposure conferred heritable changes in the binding topology of key epigenetic regulators including ATRX, SUV39H1/H2, and HP1BP3 that are preserved in untreated progeny, resulting in sustained downregulation of proliferation genes and reduced cell growth. The combination of GEN and SFN is also effective in downregulating hTERT levels, which is known to be activated when KLF4 binds to its promoter region. Other study reported that genistein isolated from Glycine max seed inhibited phosphorylation of cdk1, gene involved during G2/M transition and thus could function as G2 checkpoint abrogator. Genistein up-regulated ER-beta2 and ER-beta1 in T47D cells, and after treatment the ER-beta2 isoform became prevalent, while in BT20 cells it almost doubled the percent contribution of ER-beta1 and ER-beta2 to total ER-beta. In response to genistein, the level of BRCA1, TNF (P,0.001), BARD1, p53, pS2, jun, BAX, BAP1 and BARD1 (P,0.05) mRNAs were significantly increased in comparison with control values. BRCA2 mRNA was significantly decreased. GEN-induced apoptosis in MCF-7 cells was concomitant with increased PTEN expression, and this was abrogated by PTEN siRNA. | |
| Target pathways | p53-independent pathway IGF-I signaling pathway insulin-like growth factor signaling pathway ERK5 MAPK signaling transduction pathway ERβ pathway | |
| IC50 | 175 μM against MCF-7 49.49 μM against MCF-7 for 48h 8.8 μM against MDA-MB-468 47.50 μM against MDA-MB-231 | |
| Potency | However, in mammalian assay, apigenin was found to be more ERbeta-selective than genistein, which has equal potency in inducing transactivation through ERalpha and ERbeta. Our study revealed that the relative estrogenic potency of the substances was E2 > genistein > naringenin. The proliferative potency of these compounds in the MCF-7 cells derived from their EC(50)s decreased in the following order: estadiol (4*10(-3) nM)>biochanin A (9 nM)>genistein (32 nM)>testosterone (46 nM)>naringenin (287 nM)>apigenin (440 nM)>chrysin (4 microM). The potency to inhibit aromatase derived from their IC(50)s decreased in the following order: chrysin (1.5 microM)>naringenin (2.2 microM)>genistein (3.6 microM)>apigenin (4.1 microM)>biochanin A (25 microM)>quercetin (30 microM). The rank order potency (E2 > genistein > daidzein) is maintained in MCF-7 cells as well as G-292 cells with both receptor subtypes, with a strong receptor selectivity of the phytoestrogens for ERbeta1 over ERalpha. The rank order of inhibitory potency was naringin > rutin > alpha-tocopheryl succinate (alpha-TOS) > lovastatin > apigenin > genistein > alpha-tocopherol >or= kaempferol > gamma-tocopherol, chrysin and curcumin were inactive except at a concentration of 100 micromol/L. | |
| Cell line/ mice model | MCF-7, MDA-MB-231, SK-N-SH, MDA-MB-468, T47D, MCF-12A, HepG2, PC12, BT-549, MDA-MB-435, G-292, SKBR-3, MMTV-Wnt-1 , BT-20, MDA468, GLC4/ADR, SW-1573/2R120, HT1080/DR4, MCF-7/Mitox, HL60/ADR, UACC-3199, MCF-10F, MDA-MB-435, Hs578t, | |
| Additional information | Decreases expression of ERK5 and increases those of Bax and Caspase3 (MDA-MB-231 cells) Causes upregulation of mir-23b (MCF-7) Decreases the content of ER protein in the breast cancer cells (MCF-7) Induces cell cycle arrest at G(2)/M with induction of p21(WAF1/CIP1) Upregulates Brca1 expression in WT mice Decreases estrogen level and activity, and causes down-regulation of EGFR expression in combination with TAM ( MCF-7 cells) GEN and SFN synergestically downregulate KLF4 levels, which plays an important role in stem cell formation as well as hTERT levels Induces EGR-1 tumor suppressor expression and down-regulation of the protooncogene MET in immortalized human breast epithelial cells MCF-10F Causes suppression of IR-induced NFκB Downregulation of unfolded protein response (UPR) and autophagy-related genes (GRP78, IRE1α, ATF4, and Beclin-1) and genes linked to immunosuppression (TGFβ and Foxp3) and upregulation of cytotoxic T-cell marker CD8a in the tumors of the lifetime genistein group (IN VIVO) Downregulation of miR-155, upregulation of proapoptotic and anticell proliferative miR-155 targets FOXO3, PTEN, casein kinase, and p27 (in MDA-MB-435 and Hs578t cells) | |
| PubChem ID | 5280961 | |
| Additional PMIDs | 12421874 11828270 19003112 15069695 12840230 12725655 16506217 16702307 21783746 17266178 17200150 19733663 19928832 21992498 23661994 23337939 24323914 25363786 25009600 30810849 31171079 31881661 31982837 34336089 33932891 34209224 9066718 9168916 9831541 11303591 11096068 10802284 18313242 15182386 22256760 23351311 30620769 9631496 11795395 15030235 17125943 16441947 17948189 18815742 21615235 22075938 23452621 24299158 25385471 24978400 25826638 28644496 28969363 30352359 30722112 34673318 7903202 10523716 11525599 10956151 11060796 10923837 18621111 17658826 33255446 23112854 24508860 12425726 12239620 16434996 17234721 17687646 17482226 18025290 26703673 30544666 10479216 11110847 11488559 29963755 15110097 23871935 25844270 30171625 12793002 12710998 11920488 12429652 15579072 15070945 15492830 16248551 16081271 16183551 16679865 17181483 17157887 17516862 17681752 17341692 18316793 18669594 18479682 19800779 19589736 19603405 19115854 19918100 19073877 20554748 20661825 20164315 21097717 19924815 21462322 20707345 21397020 21680703 21712365 21828252 22864686 23342141 23379261 23645249 25410431 26179608 25781341 26771440 29051735 29955703 29899271 31078816 31751581 31786350 31652854 34836197 7833143 9679118 8910911 8891338 9168007 8896889 9809990 10566643 10704911 10993028 11509969 10945618 10867033 17051425 22219179 11062152 12881020 15686114 12628503 15323430 15284389 16152973 15905199 16619504 16469160 16758967 16596234 17052999 16338062 17579892 17976513 26059153 19286049 19013426 19159489 19321580 19566600 20517637 24200780 24532317 25493176 28148690 29981677 30737644 31950019 32895205 34413161 8886128 9343831 8970179 33527240 24325455 9770719 24260594 30684530 19298253 25934515 12929590 15077059 16081670 22227334 9607569 10679229 22339411 14556117 12066207 12879015 15126563 15205350 15113976 16777995 16515472 16846465 17961621 19592245 19996686 22071170 23189742 23973682 26199568 34698063 1279187 7794275 9381980 9492340 10427135 10340389 10601582 9849427 17132221 32191449 31192773 8545857 8105867 9631496 | |
| Additional sources of information | https://powo.science.kew.org/taxon/urn:lsid:ipni.org:names:496408-1 | |
| Safety | NA |