Sodium valproate induces mitochondria-dependent apoptosis in human hepatoblastoma cells
Wei Wang1, Xiao-li Liao, Jing-hong Chen
1Department of Biochemistry, Medical College of Jinan University, Guangzhou, Guangdong 510632, China.
Background:
Sodium valproate inhibits proliferation in neuroblastoma and glioma cells, and inhibits proliferation and induces apoptosis in hepatoblastoma cells. Information describing the molecular pathways of the antitumor effects of sodium valproate is limited; therefore, we explored the mechanisms of action of sodium valproate in the human hepatoblastoma cell line, HepG2.
Methods:
The effects of sodium valproate on the proliferation of HepG2 cells were evaluated by the Walsh-schema transform and colony formation assays. Sodium valproate-induced apoptosis in HepG2 cells was investigated with fluorescence microscopy to detect morphological changes; by flow cytometry to calculate DNA ploidy and apoptotic cell percentages; with Western blotting analyses to determine c-Jun N-terminal kinases (JNK), p-JNK, Bcl-2, Bax, and caspase-3 and -9 protein expression levels; and using JC-1 fluorescence microscopy to detect the membrane potential of mitochondria. Statistical analyses were performed using one-way analysis of variance by SPSS 13.0 software.
Results:
Our results indicated that sodium valproate treatment inhibited the proliferation of HepG2 cells in a dose-dependent manner. Sodium valproate induced apoptosis in HepG2 cells as it: caused morphologic changes associated with apoptosis, including condensed and fragmented chromatin; increased the percentage of hypodiploid cells in a dose-dependent manner; increased the percentage of annexin V-positive/propidium iodide-negative cells from 9.52% to 74.87%; decreased JNK and increased phosphate-JNK protein expression levels; reduced the membrane potential of mitochondria; decreased the ratio of Bcl-2/Bax; and activated caspases-3 and -9.
Conclusion:
Sodium valproate inhibited the proliferation of HepG2 cells, triggered mitochondria-dependent HepG2 cell apoptosis and activated JNK.
Insights
Sodium valproate inhibits hepatoblastoma cell proliferation and induces apoptosis. This study explored its molecular mechanisms, revealing effects on JNK signaling and mitochondrial pathways in HepG2 cells.
Area of Science:
- Oncology
- Molecular Biology
- Cell Biology
Background:
- Sodium valproate demonstrates antiproliferative and pro-apoptotic effects in various cancer cells.
- Limited information exists regarding the specific molecular pathways underlying sodium valproate's antitumor activity.
- This study investigates sodium valproate's mechanisms in the human hepatoblastoma cell line, HepG2.
Purpose of the Study:
- To elucidate the molecular mechanisms of sodium valproate's antitumor effects.
- To investigate the impact of sodium valproate on proliferation and apoptosis in HepG2 cells.
- To identify key signaling pathways and cellular processes affected by sodium valproate.
Main Methods:
- Cell proliferation was assessed using Walsh-schema transform and colony formation assays.
- Apoptosis was evaluated via fluorescence microscopy, flow cytometry (DNA ploidy, annexin V/PI staining), and Western blotting for apoptosis-related proteins (Bcl-2, Bax, caspases).
- Mitochondrial membrane potential was measured using JC-1 fluorescence microscopy, and JNK pathway activation was assessed via p-JNK levels.
Main Results:
- Sodium valproate significantly inhibited HepG2 cell proliferation in a dose-dependent manner.
- Apoptosis induction was evidenced by morphologic changes, increased hypodiploid cells, and elevated annexin V-positive cells.
- Key findings include JNK pathway activation (increased p-JNK), decreased mitochondrial membrane potential, altered Bcl-2/Bax ratio, and caspase-3 and -9 activation.
Conclusions:
- Sodium valproate effectively inhibits hepatoblastoma cell proliferation.
- The drug triggers mitochondria-dependent apoptosis in HepG2 cells.
- Activation of the JNK signaling pathway is a key mechanism involved in sodium valproate's action.
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