Molecular mechanisms of quinalizarin induces apoptosis and G0/G1 cell cycle of human esophageal cancer HCE-4 cells depends on MAPK, STAT3, and NF-κB signaling pathways.

Quinalizarin (Quina) is one of the main components of many herbal medicines and has good anti-tumor activity. However, the exact mode of cytotoxic action and signaling pathways on Quina in human esophageal cancer has not yet been confirmed. In this study, we explored the anticancer effect of Quina against human esophageal cancer HCE-4 cells and the underlying mechanisms. The results of the Cell Counting Kit-8 (CCK-8) assay showed that Quina inhibited the viability of human esophageal cancer HCE-4 cells in a dose-dependent and time-dependent manner. It also inhibited HCE-4 cells proliferation and induced apoptosis by increasing the levels of Bad, caspase-3, and PARP, decreasing the level of Bcl-2. The results of the cell cycle analysis suggested that Quina arrested HCE-4 cells in the G0/G1 cycle by downregulating cyclin-dependent (CDK) 2/4, cyclin D1/E and upregulating the levels of p21 and p27. We also found that Quina activated mitogen-activated protein kinase (MAPK) and inhibited the signal transducer and activator of transcription-3 (STAT3) and nuclear factor kappa B (NF-κB) signaling pathways. Furthermore, Quina significantly increased intracellular reactive oxygen species (ROS) level. The pretreatment of N-acetyl-L-cysteine (NAC) blocked the apoptosis induced by Quina and inhibited the activities of MAPK, STAT3, and NF-κB signaling pathways. These results indicate that Quina induces the apoptosis in HCE-4 cells, which is via accumulating ROS generation and regulating MAPK, STAT3, and NF-κB. In conclusion, this study demonstrated that Quina have good therapeutic effects on human esophageal cancer cells.

Quinalizarin induces ROS­mediated apoptosis via the MAPK, STAT3 and NF­κB signaling pathways in human breast cancer cells.

Quinalizarin has been demonstrated to exhibit potent antitumor activities in lung cancer and gastric cancer cells, but currently, little is known regarding its anticancer mechanisms in human breast cancer cells. The aim of the present study was to investigate the apoptotic effects of quinalizarin in MCF­7 cells and to analyze its molecular mechanisms. The MTT assay was used to evaluate the viability of human breast cancer cells that had been treated with quinalizarin and 5­fluorouracil. Flow cytometric analyses and western blotting were used to investigate the effects of quinalizarin on apoptosis and cycle arrest in MCF­7 cells with focus on reactive oxygen species (ROS) production. The results demonstrated that quinalizarin exhibited significant cytotoxic effects on human breast cancer cells in a dose­dependent manner. Accompanying ROS, quinalizarin induced MCF­7 cell mitochondrial­associated apoptosis by regulating mitochondrial­associated apoptosis, and caused cell cycle arrest at the G2/M phase in a time­dependent manner. Furthermore, quinalizarin can activate p38 kinase and JNK, and inhibit the extracellular signal­regulated kinase, signal transducer and activator of transcription 3 (STAT3) and NF­κB signaling pathways. These effects were blocked by mitogen­activated protein kinase (MAPK) inhibitor and N­acetyl­L­cysteine. The results from the present study suggested that quinalizarin induced G2/M phase cell cycle arrest and apoptosis in MCF­7 cells through ROS­mediated MAPK, STAT3 and NF­κB signaling pathways. Thus, quinalizarin may be useful for human breast cancer treatment, as well as the treatment of other cancer types.

Glycitein induces reactive oxygen species-dependent apoptosis and G0/G1 cell cycle arrest through the MAPK/STAT3/NF-κB pathway in human gastric cancer cells.

Glycitein is an isoflavone that reportedly inhibits the proliferation of human breast cancer and prostate cancer cells. However, its anti-cancer molecular mechanisms in human gastric cancer remain to be defined. This study evaluated the antitumor effects of glycitein on human gastric cancer cells and investigated the underlying mechanisms. We used MTT assay, flow cytometry and western blotting to investigate its molecular mechanisms with focus on reactive oxygen species (ROS) production. Our results showed that glycitein had significant cytotoxic effects on human gastric cancer cells. Glycitein markedly decreased mitochondrial transmembrane potential (ΔΨm) and increased AGS cells mitochondrial-related apoptosis, and caused G0/G1 cell cycle arrest by regulating cycle-related protein. Mechanistically, accompanying ROS, glycitein can activate mitogen-activated protein kinase (MAPK) and inhibited the signal transducer and activator of transcription 3 (STAT3) and nuclear factor-kappaB (NF-κB) signaling pathways. Furthermore, the MAPK signaling pathway regulated the expression levels of STAT3 and NF-κB upon treatment with MAPK inhibitor and N-acetyl-L-cysteine (NAC). These findings suggested that glycitein induced AGS cell apoptosis and G0/G1 phase cell cycle arrest via ROS-related MAPK/STAT3/NF-κB signaling pathways. Thus, glycitein has the potential to a novel targeted therapeutic agent for human gastric cancer.