O-Alkylated derivatives of quercetin induce apoptosis of MCF-7 cells via a caspase-independent mitochondrial pathway

Chem Biol Interact. 2015 Dec 5:242:91-8. doi: 10.1016/j.cbi.2015.09.022. Epub 2015 Sep 28.

Abstract

The aim of this study was to investigate the antitumor effects of two novel alkylated derivatives of quercetin, 7-O-butylquercetin (BQ) and 7-O-geranylquercetin (GQ), in MCF-7 human breast cancer cells and explore the possible cellular mechanism of the related apoptotic effects. Our data showed that BQ and GQ were more toxic to MCF-7 cells and had better accumulation ability in MCF-7 cells than quercetin. Morphological observations and DNA fragmentation pattern suggested that the derivatives could induce apoptosis in MCF-7 cells. Derivatives-induced apoptosis could not be reversed by Z-VAD-FMK and N-acetyl cysteine demonstrated that the apoptosis was independent on caspase and reactive oxygen species. Western blot assay showed that endonuclease G and apoptosis inducing factor might be relative to the apoptosis. Alkylation of quercetin at 7-O position can enhance the apoptosis inducing effect and cell accumulation ability relative to quercetin. This structural alteration brings changes on apoptosis pathway as well.

Keywords: Alkylated quercetin derivatives; Apoptosis; Apoptosis inducing factor; Breast cancer; Endonuclease G.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / drug effects*
  • Apoptosis Inducing Factor / metabolism
  • Caspases / metabolism
  • Drug Screening Assays, Antitumor / methods
  • Endodeoxyribonucleases / metabolism
  • Endoplasmic Reticulum / drug effects
  • Humans
  • MCF-7 Cells / drug effects
  • Mitochondria / drug effects
  • Mitochondria / metabolism
  • Quercetin / analogs & derivatives
  • Quercetin / chemistry
  • Quercetin / pharmacology*
  • Reactive Oxygen Species / metabolism

Substances

  • 7-O-butylquercetin
  • 7-O-geranylquercetin
  • AIFM1 protein, human
  • Apoptosis Inducing Factor
  • Reactive Oxygen Species
  • Quercetin
  • Endodeoxyribonucleases
  • endonuclease G
  • Caspases