Effect of liquiritigenin, a flavanone existed from Radix glycyrrhizae on pro-apoptotic in SMMC-7721 cells.
Liquiritigenin is a flavanone existed in Radix glycyrrhizae. The objective of this study is to explore the effects of liquiritigenin on SMMC-7721 cells and its possible mechanism. The viability of liquiritigenin treat cells was decreased in a dose-dependent manner assayed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenylterazolium bromide (MTT), and apoptotic morphological changes also be observed, such as chromatin condensation and nuclear fragmentation. Assessment of apoptotic cells by flow cytometry indicated that cells fell into apoptosis after 0.4mM liquiritigenin treatment. In addition, a concomitant time-dependent increase in caspase-3 activity was also observed. The level of p53 protein increased and Bcl-2 protein decreased time-dependently. Further studies found the induction of apoptosis by liquiritigenin was accompanied with the production of reactive oxygen species (ROS), disruption of mitochondrial membrane potential and depletion of antioxidant enzymes. The significant ROS generation was firstly found at 3h and being time-dependent until 9h. A time-dependent decrease in membrane potential occurred, and significant loss appeared at 9h and 12h. Furthermore, pretreatment of N-acetyl-cysteine (NAC), ROS production and apoptosis induced by liquiritigenin were both suppressed. In sum, this paper indicated the cytotoxicity of liquiritigenin on SMMC-7721 cells may via effect on generation of ROS, later lead to cell apoptosis.
Zhang
Shi-ping
SP
Department of Nutrition and Food Hygiene, School of Public Health, Nanjing Medical University, Nanjing, China.
Zhou
Yi-jing
YJ
Liu
Yan
Y
Cai
Yun-qing
YQ
D000111:Acetylcysteine / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D044950:Flavanones / Q000494:pharmacology*; D005434:Flow Cytometry; D005979:Glutathione Peroxidase / Q000378:metabolism; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis; D017382:Reactive Oxygen Species / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000032:analysis
D044950:Flavanones; D019253:Proto-Oncogene Proteins c-bcl-2; D017382:Reactive Oxygen Species; D016159:Tumor Suppressor Protein p53; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D053148:Caspase 3; C083152:liquiritigenin; D000111:Acetylcysteine