Anti-apoptotic effect of hepatocyte growth factor from actinomycin D in hepatocyte-derived HL7702 cells is associated with activation of PI3K/Akt signaling.
Toxicol Lett
; 165(2): 142-8, 2006 Aug 20.
Article
in En
| MEDLINE
| ID: mdl-16616440
ABSTRACT
Actinomycin D (ActD) is a well-known cytotoxic chemotherapeutic reagent and the prevention of ActD-induced apoptotic cell death has been an attractive issue for biomedical investigators. Since phosphatidylinositol-3 kinase (PI3K)/Akt pathway is essential for cell survival, the present study has examined whether the preventive effect of hepatocyte growth factor (HGF) on ActD-induced apoptotic cell death in a human hepatocyte-derived cell line (HL7702) is associated with PI3K/Akt activation. Apoptotic cell death was measured by several methods including Hoechst 33342 staining, DNA fragmentation, and flow cytometry. We found that ActD caused a significant increase in apoptotic cell death, an effect significantly prevented by pre-addition of HGF in the cultures. HGF was found to significantly activate Akt phosphorylation while pre-treatment with PI3K specific inhibitor wortmannin further enhanced ActD-induced apoptotic effect, and also significantly prevented HGF's protection against ActD-induced apoptosis. These results suggest that HGF's prevention of ActD-induced apoptotic cell death in HL7702 cells is associated with the activation of PI3K/Akt signaling.
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Database:
MEDLINE
Main subject:
Protein Synthesis Inhibitors
/
Hepatocyte Growth Factor
/
Apoptosis
/
Phosphatidylinositol 3-Kinases
/
Hepatocytes
/
Dactinomycin
Type of study:
Risk_factors_studies
Limits:
Humans
Language:
En
Year:
2006
Type:
Article