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.
journal_name
Toxicol Lettjournal_title
Toxicology lettersauthors
Li W,Cai S,Cai L,Li Xdoi
10.1016/j.toxlet.2006.02.006subject
Has Abstractpub_date
2006-08-20 00:00:00pages
142-8issue
2eissn
0378-4274issn
1879-3169pii
S0378-4274(06)00077-4journal_volume
165pub_type
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