ABSTRACT
Objective: To investigate the effect of L-asparaginase on the proliferation, cell cycle, and apoptosis of Burkitt lymphoma cell lines and explore the molecular mechanism. Methods: The effect of L-asparaginase on the cell proliferation of Burkitt lymphoma cell lines was detected using the CCK-8 method. The apoptosis rate and cell cycle were detected using flow cytometry. The expression of related molecules in cell cycle, apoptosis, autophagy, and PI3K/Akt/mTOR signaling pathway was detected and analyzed using qPCR and Western blot assay. Results: L-asparaginase significantly inhibited the proliferation of Burkitt lymphoma cell lines and caused cell cycle arrest at G(0)/G(1) phage. L-asparaginase induced cell apoptosis and autophagy in Burkitt lymphoma cell lines. Further results showed that L-asparaginase inhibited the expression of c-Myc and also inhibited the expression of p-PI3K, p-Akt-S473, p-mTOR, p-70S6K, and p-4E-BP1. Combining PI3K inhibitor LY294002 with L-asparaginase further induced apoptosis. Additionally, L-Asp inhibited STAT and ERK signaling pathways. Conclusion: L-asparaginase inhibited Burkitt lymphoma cell proliferation, arrested cell cycle, activated autophagy, and induced apoptosis by inhibiting the PI3K/Akt/mTOR signaling pathway.
Subject(s)
Asparaginase , Burkitt Lymphoma , Apoptosis , Asparaginase/pharmacology , Cell Cycle , Cell Line , Cell Line, Tumor , Cell Proliferation , Humans , Phosphatidylinositol 3-Kinases , Proto-Oncogene Proteins c-aktABSTRACT
The objective of this study was to assess the protective effects of Ginkgo biloba leaf extracts (EGb) on trichloroethylene (TCE)-induced cytotoxicity and apoptosis in normal human epidermal keratinocytes (NHEK). Cytotoxicity was determined by neutral red uptake, and lipid peroxidation of the cells was assessed by malondialdehyde (MDA) and superoxide dismutase (SOD). Electron microscopy and flow cytometry were used to evaluate NHEK apoptosis. Treatment of NHEK with various concentrations of TCE caused a substantial decrease in cell viability. NR(50 )from the cytotoxicity assay was found to be 4.53 mM. TCE caused an increase in MDA, while an inhibition of SOD activity, in a concentration-dependent manner. Electron microscopic examination revealed typical morphologic changes of apoptosis in cells treated with TCE. Incubation of NHEK with TCE (0, 0.125, 0.5, 2.0 mM) for 4 h increased the proportion of apoptotic cells from control of 19.23% to nearly 44.35%. Pretreatment of EGb at 10-200 mg/l dose-dependently attenuated the cytotoxic effect of TCE, prevented TCE-induced elevation of lipid peroxidation and decline of antioxidant enzyme activities. Similar inhibition by EGb on TCE-mediated NHEK apoptosis was also observed. These results suggest that EGb can protect NHEK from TCE-induced cytotoxicity and apoptosis, which may be associated with the superoxide scavenging effect and enhancement of antioxidant enzyme activities.
Subject(s)
Apoptosis/drug effects , Environmental Pollutants/toxicity , Ginkgo biloba , Keratinocytes/drug effects , Trichloroethylene/toxicity , Cell Survival/drug effects , Dose-Response Relationship, Drug , Humans , In Vitro Techniques , Keratinocytes/metabolism , Lipid Peroxidation/drug effects , Male , Oxidative Stress/drug effects , Plant Extracts/pharmacology , Plant LeavesABSTRACT
Shenjincao injection is a traditional Chinese medicine prepared from Palhinhaea cernua (L.) A. Franco et Vasc. by ultrafiltration. Its anti-silicosis action has been investigated both as a prophylactic and for treatment of the disease. Wistar rats were injected intra-tracheally with quartz dust and then divided randomly into groups-treatment and control prophylactic groups and treatment and control disease groups. After five days or eight weeks, respectively, the silica-exposed rats of the two treatment groups were injected intraperitoneally three times a week with shenjincao injection, dose 2.0 mL, for five weeks or 11 weeks, respectively. The rats were then dissected, and the ceruloplasmin content of the serum and the fresh weight, dry weight, collagen content and pathological grade of the lungs were measured. Compared with the corresponding exposed control groups for the same treatment periods the values of these parameters were reduced by 62.8% to 30.7% for rats in the prophylactic treatment group (P < 0.01 for all) and by 50.8% to 30.2% for the diseased group (P < 0.01 for all). The values for the disease-treatment group were also reduced by 37.9% to 25.9% compared with values for the exposed control group before treatment (P < 0.01 or P < 0.05). The effective coefficients for prophylactic treatment were 82.6% to 56.0%; for disease treatment they were 68.8% to 39.8%. These results show that shenjincao injection is efficacious against experimental silicosis not only when used prophylactically but also when used to treat the disease.
