Document Detail


Oridonin induces G2/M cell cycle arrest and apoptosis through MAPK and p53 signaling pathways in HepG2 cells.
MedLine Citation:
PMID:  20664969     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Oridonin, the main active constituent of Isodon rubescen, has antihepatocarcinoma activity in experimental and clinical settings. The aims of the study were to explore the anticancer effect of oridonin in HepG2 cells and to investigate the underlying mechanisms. Results showed that oridonin treatment for 24 or 48 h resulted in a marked decrease in cell viability time- and dose-dependently. IC50 values were determined as 38.86 microM and 24.90 microM for 24-h and 48-h treatments, respectively. Flow cytometric analysis showed that a 24-h treatment of 40 microM oridonin induced G2/M cell cycle arrest and apoptosis. Typical apoptotic nucleus alterations were observed with fluorescence microscope after DAPI staining. Immunoblot analysis demonstrated that oridonin treatment increased expression levels of p-JNK, p-p38, p-p53 and p21, elevated the level of cyclin B1/p-Cdc2 (Tyr15) complex, and inhibited the expression of p-ERK. Moreover, oridonin treatment activated caspase-9 and caspase-3. In conclusion, oridonin induced G2/M cell cycle arrest and apoptosis in HepG2 cells through MAPK and p53 pathways, which advances our understanding on the molecular mechanisms of oridonin in hepatocarcinoma management.
Authors:
Hui Wang; Yan Ye; Jian-Hong Chui; Guo-Yuan Zhu; Ying-Wei Li; David W F Fong; Zhi-Ling Yu
Related Documents :
1984409 - Correlation of metabolic stability and altered quaternary structure of oncoprotein p53 ...
15681459 - Inhibition of cell division by the human cytomegalovirus ie86 protein: role of the p53 ...
7488939 - Marker genes for cytotoxic exposure: p53.
15805289 - Rna silencing of checkpoint regulators sensitizes p53-defective prostate cancer cells t...
9488309 - Sensitization of rat glioblastoma multiforme to cisplatin in vivo following restoration...
19464429 - A nuclear budding mechanism in transiently arrested cells generates drug-sensitive and ...
19939939 - Conditional mutation of pkd2 causes cystogenesis and upregulates beta-catenin.
7578419 - Fluorescence-based selection of retrovirally transduced cells in the absence of a marke...
15338009 - The contribution of spike threshold to the dichotomy of cortical simple and complex cells.
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Oncology reports     Volume:  24     ISSN:  1791-2431     ISO Abbreviation:  Oncol. Rep.     Publication Date:  2010 Sep 
Date Detail:
Created Date:  2010-07-28     Completed Date:  2010-11-23     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9422756     Medline TA:  Oncol Rep     Country:  Greece    
Other Details:
Languages:  eng     Pagination:  647-51     Citation Subset:  IM    
Affiliation:
Center for Cancer and Inflammation Research, School of Chinese Medicine, Hong Kong Baptist University, Kowloon Tong, Hong Kong, PR China.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
Antineoplastic Agents, Phytogenic / pharmacology*
Apoptosis / drug effects*
Carcinoma, Hepatocellular / enzymology,  pathology*
Caspase 3 / metabolism
Caspase 9 / metabolism
Cell Cycle / drug effects*
Cell Division
Cell Survival / drug effects
Cyclin B / metabolism
Cyclin B1 / metabolism
Cyclin-Dependent Kinase Inhibitor p21 / metabolism
Diterpenes, Kaurane / pharmacology*
Dose-Response Relationship, Drug
Extracellular Signal-Regulated MAP Kinases / metabolism
G2 Phase
Hep G2 Cells
Humans
Inhibitory Concentration 50
JNK Mitogen-Activated Protein Kinases / metabolism
Liver Neoplasms / enzymology,  pathology*
MAP Kinase Signaling System / drug effects*
Phosphorylation
Time Factors
Tumor Suppressor Protein p53 / metabolism*
p38 Mitogen-Activated Protein Kinases / metabolism
Chemical
Reg. No./Substance:
0/Antineoplastic Agents, Phytogenic; 0/CCNB1 protein, human; 0/CDC2 protein, human; 0/CDKN1A protein, human; 0/Cyclin B; 0/Cyclin B1; 0/Cyclin-Dependent Kinase Inhibitor p21; 0/Diterpenes, Kaurane; 0/TP53 protein, human; 0/Tumor Suppressor Protein p53; 28957-04-2/oridonin; EC 2.7.11.24/Extracellular Signal-Regulated MAP Kinases; EC 2.7.11.24/JNK Mitogen-Activated Protein Kinases; EC 2.7.11.24/p38 Mitogen-Activated Protein Kinases; EC 3.4.22.-/CASP3 protein, human; EC 3.4.22.-/CASP9 protein, human; EC 3.4.22.-/Caspase 3; EC 3.4.22.-/Caspase 9

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


Previous Document:  Proteomic screening of completely resected tumors in relation to survival in patients with stage I n...
Next Document:  Evaluation of ERalpha, PR and ERbeta isoforms in neoadjuvant treated breast cancer.