Inactivation of NF-κB by genistein is mediated via Akt signaling pathway in breast cancer cells

Abstract

Genistein, a natural isoflavonoid found in soybean products, has been proposed to be associated with a lower rate of breast cancer in Asian women. Studies from our laboratory and others have shown that genistein can induce apoptosis by regulating the expression of apoptosis-related genes in breast cancer cells. However, the precise molecular mechanism(s) by which genistein induces apoptotic cell death is not clear. In order to investigate such mechanism, we tested the role of Akt and NF-jB in genistein-treated MDA-MB-231 breast cancer cells. We found that inhibition of cell growth and induction of apoptosis by genistein are partly mediated through the downregulation of Akt and NF-jB pathways. Gel shift assay showed that NF-jB DNA-binding activity in MDA-MB-231 cells transfected with Akt cDNA was induced, suggesting that there is a cross-talk between NFjB and Akt signaling pathway. Moreover, we found that genistein could abrogate EGF and Akt induced NF-jB activation. From these results, we conclude that the inactivation of NF-jB 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.

Retracted: Inhibition of nuclear factor κb activity by genistein is mediated via Notch‐1 signaling pathway in pancreatic cancer cells

“…[5][6][7][8][9][10] Our previous studies also showed that genistein can induce apoptosis and inhibit NF-jB activation in pancreatic cancer cells. 8,9,11 NF-jB plays important roles in the control of cell growth, differentiation, apoptosis and inflammation. 12 NF-jB mediates survival signals that inhibit apoptosis and promote cancer cell growth.…”

Astragali Radix elicits anti-inflammation via activation of MKP-1, concomitant with attenuation of p38 and Erk

“…Polyphenolic compounds from various herbs have been found to work as phytoestrogens (Mitchell et al, 2000;Gong et al, 2003;Klinge et al, 2005), antioxidants (Rüfer and Kulling, 2006), tyrosine kinase inhibitors (Kousidou et al, 2006), and anti-inflammatory compounds (Jung et al, 2007). HPLC analysis of AR displayed the presence of several secondary metabolites such as polyphenolic flavonoids including formononetin (Fig.…”

Cancer chemoprevention and chemotherapy: Dietary polyphenols and signalling pathways

“…Similarly, genistein inhibited cell growth and induced apoptosis of breast cancer cells through the down-regulation of AKT, ERK, NF-jB and AP-1 [131], which suggested that the inactivation of NF-jB is partly mediated by AKT and demonstrated the crosstalk between AKT and NF-jB pathways [131].…”