Oleanolic acid induces G₂/M phase arrest and apoptosis in human hepatocellular carcinoma Bel-7402 cells.
- Author:
Ling LIU
;
Jian-long ZHAO
;
Jian-gang WANG
- Publication Type:Journal Article
- MeSH:
Apoptosis;
drug effects;
Carcinoma, Hepatocellular;
drug therapy;
pathology;
Cell Line, Tumor;
G2 Phase Cell Cycle Checkpoints;
drug effects;
Humans;
Liver Neoplasms;
drug therapy;
pathology;
M Phase Cell Cycle Checkpoints;
drug effects;
Oleanolic Acid;
pharmacology
- From:
China Journal of Chinese Materia Medica
2015;40(24):4897-4902
- CountryChina
- Language:Chinese
-
Abstract:
This study was to examine the mechanism of oleanolic acid (OA) induces G2/M phase arrest and apoptosis in human hepatocellular carcinoma Bel-7402 cells. MTT and trypan blue exclusion test assay were adopted to detect the proliferate status of cells treated with OA. We assayed the cell cycle by flow cytometry using PI staining. Apoptosis was determined by Annexin V-FITC staining and PI labeling. The expressions of cycle related proteins and apoptotic related proteins were determined by Western blot analysis. OA strongly inhibited human hepatoma cells proliferation. When Bel-7402 cells were pretreated with OA for 24 h, OA induced apoptosis and G₂/M phase cell cycle arrest in a concentration-dependent manner. Analysis of the cell cycle regulatory proteins demonstrated that OA decreased the protein levels of cyclin B1, but increased the protein levels of p-Cdk1 (Tyr15) and p-Cdc25C (Ser 216). Moreover, OA modulated the phosphorylation of protein kinases Chk1 and p2l. Western blotting assay also showed significant decrease of Bcl-2 protein expression and increase of Bax protein expression, the cytosol Cyt c level, cleaved-caspase-9 and cleaved-caspase-3 activity. These data suggest that OA produces anti-tumor effect via induction of G₂/M cell cycle arrest and apoptosis.
