ABSTRACT
A terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) assay was used to determine that apoptosis causes HeLa cell death induced by pseudolaric acid B. The c-Jun N-terminal kinase (JNK) inhibitor SP600125 decreased p53 protein expression during exposure to pseudolaric acid B. SP600125 decreased the phosphorylation of p53 during pseudolaric acid B exposure, indicating that JNK mediates phosphorylation of p53 during the response to pseudolaric acid B. SP600125 reversed pseudolaric acid B-induced down-regulation of phosphorylated extracellular signal-regulated protein kinase (ERK), and protein kinase C (PKC) was activated by pseudolaric acid B, whereas staurosporine, calphostin C, and H7 partly blocked this effect. These results indicate that p53 is partially regulated by JNK in pseudolaric acid B-induced HeLa cell death and that PKC participates in pseudolaric acid B-induced HeLa cell death.
Subject(s)
Humans , Tumor Suppressor Protein p53/metabolism , Protein Kinase C/metabolism , Phosphorylation , JNK Mitogen-Activated Protein Kinases/physiology , HeLa Cells , Diterpenes/pharmacology , DNA Fragmentation/drug effects , Cell Death/drug effects , Anthracenes/pharmacologyABSTRACT
Pseudolaric acid B was isolated from Pseudolarix kaempferi Gordon (Pinaceae) and was evaluated for the anti-cancer effect in HeLa cells. We observed that pseudolaric acid B inhibited cell proliferation and induced apoptosis in a time- and dose-dependent manner. HeLa cells treated with pseudolaric acid B showed typical characteristics of apoptosis including the morphological changes and DNA fragmentation. JNK inhibitor, SP600125, markedly inhibited pseudolaric acid B-induced cell death. In addition, Bcl-2 expression was down-regulated while Bax protein level was up-regulated. Caspase-3 inhibitor, z-DEVD-fmk, partially blocked pseudolaric acid B-induced cell death, and the expression of two classical caspase substrates, PARP and ICAD, were both decreased in a time- dependent manner, indicative of downstream caspase activation.
Subject(s)
Humans , Anthracenes/pharmacology , Apoptosis , Caspases/antagonists & inhibitors , Cell Proliferation/drug effects , Cysteine Proteinase Inhibitors/pharmacology , Diterpenes/pharmacology , Down-Regulation , Enzyme Activation , HeLa Cells , JNK Mitogen-Activated Protein Kinases/drug effects , Oligopeptides/pharmacology , Protein Kinase Inhibitors/pharmacology , Proto-Oncogene Proteins c-bcl-2/metabolism , Signal Transduction/drug effects , Up-RegulationABSTRACT
Objective To investigate the effect of Ligu Capsules in preventing and treating menopausal osteoporosis in ovariectomized rats.Methods Rat models with osteoporosis were established by ovariectomy. Bone mineral density of femur,dry and wet bone weight and blood biochemical parameters were measured before and after treatment.Results Compared with the model group, Ligu Capsules increased femur bone mineral density,elevated the serum levels of Ca,P,Mg ,Zn and CT, decreased serum BGP level and hydroxyproline/creatinine(Hyp/Crea)ratio,increased dry weight, wet weight and ash weight of femur, as well as the bone length, bone volume, and bone diameter.Conclusion Ligu Capsules can prevent and treat osteoporosis in ovariectomized rats.
ABSTRACT
AIM: To examine the apoptotic pathway of norcantharidin (NCTD)-induced HeLa cells death. METHODS: MTT, photomicroscopical observation, DNA agarose gel electrophoresis, LDH release and Western blot analysis were used. RESULTS: NCTD induced HeLa cells apoptosis and the apoptosis was partially reversed by the inhibitors of caspase-family (-3, -8, -10). The activities of caspase-3, -8 and -9 were significantly increased after treated with NCTD. The expression of the inhibitor of caspase-3 activated DNase (ICAD) was decreased in a time dependent manner. CONCLUSION: NCTD induces HeLa cells apoptosis through activating caspase pathways.