Phytochemical Name : Formononetin

Properties Information
PhytoCAT-ID PhytoCAT-1022
Phytochemical name or plant extracts Formononetin
PMID 29277346
Literature evidence Considering specific foods, an increased the risk of developing breast cancer was seen with a moderate intake of formononetin, but no significant associations were found between breast cancer risk and other isoflavone-rich diets.
IUPAC name 7-hydroxy-3-(4-methoxyphenyl)chromen-4-one
Phytochemicals’ class or type of plant extracts Flavonoid
Source of phytochemicals or plant Extracts Astragalus membranaceus
Geographical availability Altay, Amur, Buryatiya, China North-Central, China South-Central, Chita, Inner Mongolia, Irkutsk, Kazakhstan, Khabarovsk, Krasnoyarsk, Manchuria, Mongolia, Primorye, Qinghai, Sakhalin, Tibet, Tuva, West Siberia, Xinjiang, Yakutskiya
Plant parts Root
Other cancers Breast cancer, Colorectal cancer
Target gene or protein hTERT,c-MYC,Bcl-2, Ha-ras, QR, C3, COX7RP, SULT1A3, ERα, miR-375, AKT, Bcl-2, MMP2, MMP9, TIMP-1, TIMP-2, TNF-α, IL-6 and IL-1β, nitrite, PGE2, iNOS, COX-2
Gene or Protein evidence SULT1A3 was of great significance in determining sulfonation of formononetin, A collection of primary estrogen receptor (ER)-regulated genes by estradiol (E2), including hTERT, c-MYC, BCL2 and Ha-ras (oncogenic) and quinone reductase (QR), human complement 3 (C3) and COX7RP (non-oncogenic) were selected as marker genes for a MCF-7 cell-based endogenous gene expression assay. After treatment with formononetin, ERα, miR-375, p-Akt, and Bcl-2 expression was significantly upregulated. Collectively, these results suggest that formononetin inhibited breast cancer cell migration and invasion by reducing the expression of MMP-2 and MMP-9 through the PI3K/AKT signaling pathway. In vitro, formononetin reduced the expression of matrix metalloproteinase-2 (MMP-2), MMP-9 and increased the expression of tissue inhibitor of metalloproteinase-1 (TIMP-1) and TIMP-2. Results showed that formononetin significantly reduced the production of TNF-α, IL-6 and IL-1β, nitrite and PGE2, as well as protein levels of iNOS and COX-2.
Target pathways ERK1/2 signaling pathway Nrf2-mediated signaling pathway PI3K/AKT signaling pathway PI3K/AKT/mTOR signaling pathway ERK1/2 MAPK-Bax pathway Extracellular signal-regulated kinase1/2 (ERK1/2) mitogen-activated protein kinase (MAPK) signaling pathway Insulin-like growth factor 1(IGF1)/IGF1R-phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) pathway Ras-p38MAPK pathway
IC50 NA
Potency These findings demonstrate a potentially new therapeutic strategy of formononetin as anti-invasive agent for breast cancer.
Cell line/ mice model MCF-7, MDA-MB-231, 4T1, ER-positive MCF-7, T47D, Caco-2, SKBR-3, HUVEC, LNCaP, PC-3
Additional information  Exhibits the anti-estrogenic effects on E2-induced transcriptions of marker genes including hTERT, c-MYC, BCL2 and Ha-ras (oncogenic) and quinone reductase (QR), human complement 3 (C3) and COX7RP (non-oncogenic) Modulates ERβ and increases luciferase activity in MCF7 breast cancer cells with limited proliferative effect Enhances the antiproliferative effects of epirubicin in MDA-MB-231 cell line Enhances the effect of epirubicin in multidrug resistance protein (MRP)-expressing human breast cancer cell line MDA-MB-231
PubChem ID 5280378
Additional PMIDs 15069695 15876415 19928832 22828872 29913427 9704568 22328166 24488720 9631496 16773531 24056502 28105248 29523109 33424409 19847742 24508860 24067281 23286459 29277346 23982890 26059153 21943063 24977660 25613180 25663261 30243825 33510641 15796199 30551465
Additional sources of information https://powo.science.kew.org/taxon/urn:lsid:ipni.org:names:478611-1
Safety MTT assay and MAP2 immunoreactivity experiments showed that formononetin produced significant neuroprotective activity by preventing BV2 microglia conditioned media-induced toxicity to HT22 neurons.