Anthraquinone compounds have been shown to induce apoptosis in different cancer cell types. Effects of chrysophanol, an anthraquinone compound, on cancer cell death have not been well-studied. The goal of this study was to examine if chrysophanol had cytotoxic effects and if such effects involved apoptosis or necrosis in J5 human liver cancer cells. Chrysophanol induced necrosis in J5 cells in a dose- and time-dependent manner. Non-apoptotic cell death was induced by chrysophanol in J5 cells and was characterized by caspase independence, delayed externalization of phosphatidylserine and plasma membrane disruption. Blockage of apoptotic induction by a general caspase inhibitor (z-VAD-fmk) failed to protect cells against chrysophanol-induced cell death. The levels of ROS production and loss of mitochondrial membrane potential (ΔΨm) were also determined to assess the effects of chrysophanol. However, reductions in ATP levels and increases in LDH activity indicated that chrysophanol stimulated necrotic cell death. In summary, human liver cancer cells treated with chrysophanol exhibited a cellular pattern associated with necrosis and not apoptosis.

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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.

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 Ca2+ levels and reduced the mitochondrial membrane potential (ΔΨm). 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.

Several studies have shown that gallic acid (GA) induces apoptosis in different cancer cell lines, whereas the mechanism of action of GA-induced apoptosis at the molecular level in human non-small-cell lung cancer NCI-H460 cells is not well-known. Here, GA decreasing the percentage of viable NCI-H460 cells was investigated; GA-induced apoptosis involved G2/M phase arrest and intracellular Ca(2+) production, the loss of mitochondrial membrane potential (DeltaPsi(m)), and caspase-3 activation. The efficacious induction of apoptosis and DNA damage was observed at 50-500 microM for 24 and/or 48 h as examined by flow cytometry, DAPI staining, and Comet assay methods. Western blotting and flow cytometric analysis also demonstrated that GA increased protein levels of GADD153 and GRP78, activation of caspase-8, -9, and -3, loss of DeltaPsi(m) and cytochrome c, and AIF release from mitochondria. Moreover, apoptosome formation and activation of caspase cascade were associated with apoptotic cell death. GA increased Bax and Bad protein levels and decreased Bcl-2 and Bcl-xL levels. GA may also induce apoptosis through a caspase-independent AIF pathway. In nude mice bearing NCI-H460 xenograft tumors, GA inhibited tumor growth in vivo. The data suggest that GA induced apoptosis in NCI-H460 lung cancer cells via a caspase-3 and mitochondrion-dependent pathway and inhibited the in vivo tumor growth of NCI-H460 cells in xenograft models.