Quercetin-mediated cell cycle arrest and apoptosis involving activation of a caspase cascade through the mitochondrial pathway in human breast cancer MCF-7 cells

Abstract

Dietary polyphenols have been correlated with a reduced risk of developing cancer. Quercetin (a natural polyphenolic compound) induced apoptosis in many human cancer cell lines, including breast cancer MCF-7 cells. However, the involvement of possible signaling pathways and the roles of quercetin in apoptosis are still undefined. The purpose of this study was to investigate the effects of quercetin on the induction of the apoptotic pathway in human breast cancer MCF-7 cells. When MCF-7 cells were treated with quercetin for 24 and 48 h and at various doses (10-175 microM), cell viability decreased significantly in time- and dose-dependent manners. Exposure of MCF-7 cells to 10-175 microM quercetin resulted in an approximate 90.25% decrease in viable cells. To explicate the mechanism underlying the antiproliferative effect of quercetin, cell cycle distribution and apoptosis in MCF-7 cells was investigated after exposure to 150 microM quercetin for 6-48 h. Quercetin caused a remarkable increase in the number of S phase (14.56% to 61.35%) and sub-G1 phase cells (0.1% to 8.32%) in a dose- and time-dependent manner. Quercetin caused S phase arrest by decreasing the protein expression of CDK2, cyclins A and B while increasing the p53 and p57 proteins. Following incubation with quercetin for 48 h, MCF-7 cells showed apoptotic cell death by the decreased levels of Bcl-2 protein and DeltaPsi(m) and increased activations of caspase-6, -8 and -9. Moreover, quercetin increased the AIF protein released from mitochondria to nuclei and the GADD153 protein translocation from endoplasmic reticulum to the nuclei. These data suggested that quercetin may induce apoptosis by direct activation of the caspase cascade through the mitochondrial pathway in MCF-7 cells.

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“…The treatment increased the number of S phase and sub-G 1 phase cells in a dose-and time-dependent manner. There was a decrease of protein expression of CDK2, cyclins A, Bcl-2 and B, while increasing the p53 and p57 proteins and activations of caspase-6, -8 and -9 in quercetin treated cancer cells 80 . Soyocak et al 81 studied the effect of quercetin in relation to induction of antiproliferation and apoptosis in breast cancer cell lines, on Bak protein.…”

Triphenyltin(IV) benzoates with diazenyl/imino scaffold exhibiting remarkable apoptosis mediated by reactive oxygen species

“…Based on encouraging results described above, 1, 3 and 5 were further investigated in order to record changes on the cell cycle phase distribution on the basis of DNA content in MDAB-231 and HeLa cell lines after exposure for 24 h by flow cytometry analysis using PI staining [67]. Cells were treated with the concentrations close to the IC 50 values determined for 1, 3 and 5.…”

Oridonin induces apoptosis and reverses drug resistance in cisplatin resistant human gastric cancer cells

“…Approximately 2x10 5 cells/well were added to a 12-well plate and treated with Ori (0, 20, 30, 40 µM) for 24 h. Cells in each treatment and control were then stained by DAPI, examined under fluorescence microscopy and images were captured, as previously described (16).…”