<p>Seventeen flavonoids with different substitutions were evaluated for inhibition of nuclear factor-κB (NF-κB) signaling in the invasive breast cancer cell line MDA-MB-231. They were screened using an engineered MDA-MB-231 cell line reporting NF-κB activation. The modulation of expression of two NF-κB regulated genes involved in tumorigenesis, matrix metalloproteinase-9 (MMP-9), and cyclooxygenase-2 (COX-2) were also analyzed in these cells. Among the compounds tested, all except gossypetin and quercetagetin inhibited the activation of NF-κB, and the expression of MMP-9 and COX-2 to different degree. Methylated flavone, chrysoeriol (luteolin-3′-methylether), was found to be the most potent inhibitor of MMP-9 and COX-2 expressions. The effect of chrysoeriol on cell proliferation, cell cycle, apoptosis and metastasis was analyzed by established methods. Chrysoeriol caused cell cycle arrest at G2/M and inhibited migration and invasion of MDA-MB-231 cells. The structure-activity relations amongst the flavonoids as NF-κB signaling inhibitors was studied. The study indicates differences between the actions of various flavonoids on NF-κB activation and on the biological activities of breast cancer cells. Flavones in general, were more active than the corresponding flavonols. © 2014 Elsevier Ltd. All rights reserved.</p>
cited By (since 1996)0; Article in Press
Ka Amrutha, Pandurangan Nanjan, Shaji, S. Ka, Sunilkumar, Da, Subhalakshmi, Ka, Rajakrishna, Lb, and Dr. Asoke Banerji, “Discovery of lesser known flavones as inhibitors of NF-κB signaling in MDA-MB-231 breast cancer cells-A SAR study”, Bioorganic and Medicinal Chemistry Letters, vol. 24, no. 19, pp. 4735-4742, 2014.