Discovery of lesser known flavones as inhibitors of NF-κB signaling in MDA-MB-231 breast cancer cells--A SAR study

Bioorg Med Chem Lett. 2014 Oct 1;24(19):4735-4742. doi: 10.1016/j.bmcl.2014.07.093. Epub 2014 Aug 14.

Abstract

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.

Keywords: Breast cancer; COX-2; Chrysoeriol; Metastasis; Methylated flavonoids; NF-κB.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / drug effects
  • Cell Cycle / drug effects
  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Dose-Response Relationship, Drug
  • Drug Discovery*
  • Flavones / chemical synthesis
  • Flavones / chemistry
  • Flavones / pharmacology*
  • Humans
  • Molecular Structure
  • NF-kappa B / antagonists & inhibitors*
  • NF-kappa B / metabolism
  • Signal Transduction / drug effects*
  • Structure-Activity Relationship

Substances

  • Flavones
  • NF-kappa B