ABSTRACT
AIM: The aim of this study is to investigate the mechanism of baicalein in inducing human liver cell line SMMC-7721 apoptosis. MATERIALS AND METHODS: Twenty micromoles baicalein or 10 µM LY294002 was adopted to treat SMMC-7721 cells. Cell proliferation was tested by cell counting kit-8 assay. Cell cycle was determined by flow cytometry and cyclin D1 expression. Cell apoptosis was detected by annexin V/propidium iodide double staining. Phosphatidyl inositol 3-kinase (PI3K)/Akt signaling pathway was assessed by real-time polymerase chain reaction and Western blot. RESULTS: Baicalein suppressed liver cancer cell SMMC-7721 proliferation and induced cell apoptosis together with LY294002. Baicalein blocked cell cycle in G0-G1 phase and downregulated cyclin D1 level. Baicalein and LY294002 significantly suppressed PI3K/Akt signaling pathway-related molecule activity at both mRNA and protein levels (P < 0.05). CONCLUSION: Baicalein can inhibit liver cancer cell proliferation and promote cell apoptosis by affecting PI3K/Akt signaling pathway together with LY294002.
Subject(s)
Antineoplastic Agents/pharmacology , Apoptosis/drug effects , Chromones/pharmacology , Flavanones/pharmacology , Morpholines/pharmacology , Phosphatidylinositol 3-Kinase/metabolism , Proto-Oncogene Proteins c-akt/metabolism , Signal Transduction/drug effects , Apoptosis/genetics , Cell Cycle/drug effects , Cell Line, Tumor , Cell Proliferation/drug effects , Humans , Liver Neoplasms/genetics , Liver Neoplasms/metabolismABSTRACT
Polychlorinated biphenyls (PCBs) have been reported to be associated with increased risk to hypertension, atherosclerosis, cardiovascular disease, etc. 2,3',4,4',5-Pentachlorobiphenyl, known as PCB-118, is a member of coplanar PCBs which renders their structure similar to polychlorinated dibenzo-p-dioxins (PCDDs) and has dioxin-like activity. In our current study, we investigated the effect of PCB-118 exposure on nitric oxide (NO) production and the underlying mechanisms in vitro. Exposure of PCB-118 impaired insulin-induced NO production and endothelial nitric oxide synthase (eNOS) activity in human umbilical vein endothelial cells (HUVECs) with no significant effect on cell viability. Furthermore, PCB-118 treatment induced oxidative stress. In addition, scavenging of reactive oxygen species (ROS) by 10 µM N-acetyl-l-cysteine (NAC) partly rescued impaired insulin-induced eNOS activities and NO productions induced by PCB-118 in HUVECs. Taken together, these results indicate that PCB-118 mediates lower eNOS activity and impairs insulin-induced NO production partly through excessive ROS production in endothelial cells.
Subject(s)
Endothelium, Vascular/drug effects , Insulin/pharmacology , Nitric Oxide/biosynthesis , Polychlorinated Biphenyls/toxicity , Reactive Oxygen Species/metabolism , Acetylcysteine/pharmacology , Endothelium, Vascular/metabolism , Human Umbilical Vein Endothelial Cells , HumansABSTRACT
Endothelial cell apoptosis, which may alter the integrity of the endothelium and lead to plaque instability, plays a critical role in the development and pathogenesis of atherosclerosis. Exposure of polychlorinated biphenyls (PCBs) is associated with increased risk of atherosclerosis and cardiovascular disease. In our present study, we explored whether exposure to PCB 118 influences endothelial cell apoptosis in vitro and the underlying mechanisms involved. As expected, exposure to PCB 118 increased the intracellular reactive oxygen species (ROS) levels in HUVECs. Increases in apoptosis and Bax/Bcl-2 ratios were observed in PCB 118-treated HUVECs. N-acetyl-l-cysteine (NAC), a ROS scavenger, partially reduced PCB 118-induced apoptosis and Bax/Bcl-2 ratios in HUVECs. Taken together, PCB 118-induced endothelial cell apoptosis was partially initiated by excessive ROS production.
