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

• 7-O-butylquercetin (BQ) and 7-O-geranylquercetin (GQ) were more toxic to MCF-7 cells.
• BQ and GQ had better accumulation ability in MCF-7 cells than quercetin.
• BQ and GQ induced apoptosis of MCF-7 cells via Endo G-mediated mitochondria pathway.

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.