Cancer: Prostate, colorectal., breast, cervical
Action: Cell-cycle arrest, MDR, growth-inhibitory
Estrogenic or Anti-estrogenic
Formononetin is one of the main active components of red clover plants, and considered as a phytoestrogen. Its pharmacological effects in vivo may be either estrogenic or anti-estrogenic, mainly depending upon the estrogen levels (Chen & Sun., 2012).
Cell-cycle Arrest, Prostate Cancer
Formononetin has been demonstrated to cause cell-cycle arrest at the G0/G1 phase by inactivating insulin-like growth factor 1(IGF1)/IGF1R-phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) pathway in MCF-7 cells. The molecular mechanisms involved in the effect of formononetin on prostate cancer cells were hence investigated. These results suggest that higher concentrations of formononetin inhibit the proliferation of prostate cancer cells (LNCaP and PC-3), while the most striking effect was observed in LNCaP cells.
From these results, it was concluded that the induced apoptosis effect of formononetin on human prostate cancer cells was related to ERK1/2 MAPK-Bax pathway. Considering that red clover plants were widely used clinically, these results provided the foundation for future development of different concentrations of formononetin for treatment of prostate cancer (Ye et al., 2012).
Colon Cancer
Formononetin is a novel herbal isoflavonoid isolated from Astragalus membranaceus, a medicinal plant that possesses anti-tumorigenic properties. It has been demonstrated that formononetin initiates growth-inhibitory and pro-apoptotic activities in human colon cancer cells. The potential of formononetin in controlling angiogenesis and tumor cell invasiveness has further been examined in human colon cancer cells and tumor xenografts. The results showed that formononetin downregulated the expression of the key pro-angiogenic factors, including vascular endothelial growth factor (VEGF) and matrix metalloproteinases. The tumor size and the number of proliferating cells were reduced in the tumor tissues obtained from the formononetin-treated group.
The serum VEGF level was also reduced in the drug-treated animals when compared to the controls. These findings suggest that formononetin inhibits angiogenesis and tumor cell invasion, and thus support its use in the treatment of advanced and metastatic colon cancers (Auyeung et al., 2012).
Cervical Cancer
Formononetin may potentiate the cytotoxicity of epirubicin in HeLa cells through the ROS-mediated MRP inhibition and concurrent activation of the mitochondrial and death receptor pathways of apoptosis. Hence, the circumvention of pump and non-pump resistance using formononetin and epirubicin may pave the way for a powerful chemotherapeutic regimen for treating human cervical cancer (Lo et al., 2013).
Breast Cancer
Recent studies by Chen & Sun (2012) suggest that formononetin inactivated IGF1/IGF1R-PI3K/Akt pathways and decreased cyclin D1 mRNA and protein expression in human breast cancer cells in vitro and in vivo. In their present study, they further investigated the molecular mechanisms involved in the induced apoptosis effect of formononetin on breast cancer cells and formononetin inhibited the proliferation of ER-positive MCF-7 cells and T47D cells. The induced apoptosis effect of formononetin on human breast cancer cells was related to Ras-p38MAPK pathway.
Formononetin causes cell-cycle arrest at the G0/G1 phase by inactivating IGF1/IGF1R-PI3K/Akt pathways and decreasing cyclin D1 mRNA and protein expression, indicating the use of formononetin in the prevention of breast cancer carcinogenesis (Chen et al., 2011).
References