There has been considerable evidence recently demonstrating the anti-tumour effects of
flavonols.
Quercetin, an ubiquitous bioactive
flavonol, inhibits cells proliferation, induces cell cycle arrest and apoptosis in different
cancer cell types. The precise molecular mechanism of
quercetin-induced apoptosis in human
breast cancer cells is unclear. The purpose of this study was to investigate effects of
quercetin on cell viability and to determine its underlying mechanism in human
breast cancer MDA-MB-231 cells.
Quercetin decreased the percentage of viable cells in a dose- and time-dependent manner, which was associated with cell cycle arrest and apoptosis.
Quercetin did not increase
reactive oxygen species generation but increased cytosolic Ca(2+) levels and reduced the mitochondrial membrane potential (DeltaPsi(m)).
Quercetin treatment promoted activation of
caspase-3, -8 and -9 in MDA-MB-231 cells.
Caspase inhibitors prevented the
quercetin-induced loss of cell viability.
Quercetin increased abundance of the
pro-apoptotic protein Bax and decreased the levels of
anti-apoptotic protein Bcl-2. Confocal
laser microscope examination indicated that
quercetin promoted
apoptosis-inducing factor (AIF) release from mitochondria and stimulated translocation to the nucleus. Taken together, these findings suggest that
quercetin results in human
breast cancer MDA-MB-231 cell death through mitochondrial- and caspase-3-dependent pathways.