Anti-apoptotic effect of hepatocyte growth factor from actinomycin D in hepatocyte-derived HL7702 cells is associated with activation of PI3K/Akt signaling

Toxicology Letters
Wenjun LiXiaokun Li

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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Citations

Sep 17, 2011·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Yuncheng LiWeijia Kong
Dec 4, 2012·Molecular Human Reproduction·Zhan MaChunfang Liu
Nov 7, 2012·Fitoterapia·Wei JiaoHuawu Shao
Nov 27, 2010·Biochemical and Biophysical Research Communications·Maren IlowskiWolfgang E Thasler

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